Dermatology

A 45-year-old man presented to the Dermatology Clinic with a 4-month history of a bump on his left upper back. The lesion was tender and had been draining clear fluid and intermittent blood; he denied any preceding trauma. He had been seen both by his primary care physician and by a physician at an urgent care clinic, where he was told to use an antibiotic ointment and benzoyl peroxide daily on the area and advised to seek a dermatology consult should it not resolve. He did not see any improvement from these measures.

Physical exam revealed a 0.8-cm erythematous nodule with a peripheral collarette of scale at its base. The bandage used to cover the nodule was stained with hemorrhagic crust (FIGURE 1A). Superior and medial to the new lesion was a well-healed scar overlying much of the patient’s thoracic spine (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Metastatic renal cell carcinoma

The nodule initially appeared to be a benign pyogenic granuloma. In fact, a biopsy of the nodule showed a profile similar to that of a pyogenic granuloma and it exhibited granulation tissue. However, further questioning revealed that the patient had a history of metastatic clear cell renal carcinoma. (The scar was from a prior unrelated orthopedic surgery.) Immunohistochemical stains showed positive staining in the cells of interest for PAX8 and CK8, 2 markers for renal cell lineage.

Consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy

Cutaneous metastasis to the skin is a rare event, representing roughly 2% of all skin tumors.¹ Anatomically, lesions tend to appear on the head and neck in men and anterior chest and abdomen in women.² Eruptions on the back, as seen in our patient, are relatively rare. The primary source of the metastasis also is gender dependent. Melanoma is the most common source overall; but in women, breast cancer represents the large majority of cutaneous metastases³ while in men lung, large intestine, and oral cavity tumors are the most common origin.³ Renal metastases are the fourth most common cause in men.³

The clinical morphology of cutaneous metastases is protean; the most common manifestations are nodules, papules, plaques, tumors, and ulcers.² Rare manifestations include alopecia plaques, erysipelas, herpes zoster–like eruptions,⁴ and pyogenic granuloma–like manifestations, as in our case. Pyogenic granuloma–like manifestations have been described in renal cell carcinoma, breast carcinoma, acute myelogenous leukemia,⁵ and hepatocellular carcinoma.⁶

Differential includes an array of erythematous nodules

The differential diagnosis of a lesion with the appearance of a pyogenic granuloma is ­variable.

Pyogenic granulomas tend to arise over a short period of time. They are more common in children and pregnant women. Pyogenic granulomas can manifest anywhere but often are reported on the digits and extremities. Clinical history is important to ensure no history of internal malignancy.

Continue to: Bartonella henselae

Bartonella henselae, known as “cat scratch disease,” also can present as a friable, erythematous nodule reminiscent of a pyogenic granuloma. Patients with bartonella henselae usually are immunocompromised and/or have had close contact with a cat.⁷

Kaposi sarcoma is a vascular tumor that may manifest as erythematous papules or nodules. Erythematous or violaceous patches or plaques may be present before a nodule arises. Kaposi sarcoma may manifest on the legs of elderly patients or anywhere on immunocompromised patients. Immunohistochemical stains for human herpesvirus-8 can clinch the diagnosis.⁸

Amelanotic melanoma may be impossible to discern clinically from a pyogenic granuloma. It appears as erythematous, violaceous, or flesh-colored nodules. Histologic evaluation is paramount in the diagnosis.⁹

Clinical suspicion should prompt a biopsy

The diagnosis of metastatic renal cell carcinoma is made on clinical suspicion and skin biopsy. Dermoscopy is an important tool in the evaluation of primary cutaneous tumors. Due to the rarity of cutaneous metastases, studies on dermoscopic findings in cutaneous metastases are limited to case series. One series showed a vascular dermoscopy pattern in 15 of 17 cases (88%).¹⁰

In light of this nonspecific pattern, it’s wise to consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy. Any lesion suspected of being a pyogenic granuloma that does not respond to conservative measures also would warrant a biopsy. Definitive diagnosis is made based upon histologic evaluation.

Continue to: Surgery is the cornerstone of treatment

 

 

Surgery is the cornerstone of treatment

Upon diagnosis, immediate referral for further local and systemic control is recommended. Treatment may consist of any combination of surgery, chemotherapy, immunotherapy, or radiation.¹¹

In this case, our patient was referred to Oncology for further treatment. Unfortunately, cutaneous metastases portend a very poor prognosis, with approximate survival times of 7.5 months.¹²

CORRESPONDENCE
M. Tye Haeberle, MD, 3810 Springhurst Boulevard, Ste 200, Louisville, KY 40241; tye.haeberle@gmail.com

A 45-year-old man presented to the Dermatology Clinic with a 4-month history of a bump on his left upper back. The lesion was tender and had been draining clear fluid and intermittent blood; he denied any preceding trauma. He had been seen both by his primary care physician and by a physician at an urgent care clinic, where he was told to use an antibiotic ointment and benzoyl peroxide daily on the area and advised to seek a dermatology consult should it not resolve. He did not see any improvement from these measures.

Physical exam revealed a 0.8-cm erythematous nodule with a peripheral collarette of scale at its base. The bandage used to cover the nodule was stained with hemorrhagic crust (FIGURE 1A). Superior and medial to the new lesion was a well-healed scar overlying much of the patient’s thoracic spine (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Metastatic renal cell carcinoma

The nodule initially appeared to be a benign pyogenic granuloma. In fact, a biopsy of the nodule showed a profile similar to that of a pyogenic granuloma and it exhibited granulation tissue. However, further questioning revealed that the patient had a history of metastatic clear cell renal carcinoma. (The scar was from a prior unrelated orthopedic surgery.) Immunohistochemical stains showed positive staining in the cells of interest for PAX8 and CK8, 2 markers for renal cell lineage.

Consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy

Cutaneous metastasis to the skin is a rare event, representing roughly 2% of all skin tumors.¹ Anatomically, lesions tend to appear on the head and neck in men and anterior chest and abdomen in women.² Eruptions on the back, as seen in our patient, are relatively rare. The primary source of the metastasis also is gender dependent. Melanoma is the most common source overall; but in women, breast cancer represents the large majority of cutaneous metastases³ while in men lung, large intestine, and oral cavity tumors are the most common origin.³ Renal metastases are the fourth most common cause in men.³

The clinical morphology of cutaneous metastases is protean; the most common manifestations are nodules, papules, plaques, tumors, and ulcers.² Rare manifestations include alopecia plaques, erysipelas, herpes zoster–like eruptions,⁴ and pyogenic granuloma–like manifestations, as in our case. Pyogenic granuloma–like manifestations have been described in renal cell carcinoma, breast carcinoma, acute myelogenous leukemia,⁵ and hepatocellular carcinoma.⁶

Differential includes an array of erythematous nodules

The differential diagnosis of a lesion with the appearance of a pyogenic granuloma is ­variable.

Pyogenic granulomas tend to arise over a short period of time. They are more common in children and pregnant women. Pyogenic granulomas can manifest anywhere but often are reported on the digits and extremities. Clinical history is important to ensure no history of internal malignancy.

Continue to: Bartonella henselae

Bartonella henselae, known as “cat scratch disease,” also can present as a friable, erythematous nodule reminiscent of a pyogenic granuloma. Patients with bartonella henselae usually are immunocompromised and/or have had close contact with a cat.⁷

Kaposi sarcoma is a vascular tumor that may manifest as erythematous papules or nodules. Erythematous or violaceous patches or plaques may be present before a nodule arises. Kaposi sarcoma may manifest on the legs of elderly patients or anywhere on immunocompromised patients. Immunohistochemical stains for human herpesvirus-8 can clinch the diagnosis.⁸

Amelanotic melanoma may be impossible to discern clinically from a pyogenic granuloma. It appears as erythematous, violaceous, or flesh-colored nodules. Histologic evaluation is paramount in the diagnosis.⁹

Clinical suspicion should prompt a biopsy

The diagnosis of metastatic renal cell carcinoma is made on clinical suspicion and skin biopsy. Dermoscopy is an important tool in the evaluation of primary cutaneous tumors. Due to the rarity of cutaneous metastases, studies on dermoscopic findings in cutaneous metastases are limited to case series. One series showed a vascular dermoscopy pattern in 15 of 17 cases (88%).¹⁰

In light of this nonspecific pattern, it’s wise to consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy. Any lesion suspected of being a pyogenic granuloma that does not respond to conservative measures also would warrant a biopsy. Definitive diagnosis is made based upon histologic evaluation.

Continue to: Surgery is the cornerstone of treatment

 

 

Surgery is the cornerstone of treatment

Upon diagnosis, immediate referral for further local and systemic control is recommended. Treatment may consist of any combination of surgery, chemotherapy, immunotherapy, or radiation.¹¹

In this case, our patient was referred to Oncology for further treatment. Unfortunately, cutaneous metastases portend a very poor prognosis, with approximate survival times of 7.5 months.¹²

CORRESPONDENCE
M. Tye Haeberle, MD, 3810 Springhurst Boulevard, Ste 200, Louisville, KY 40241; tye.haeberle@gmail.com

A 45-year-old man presented to the Dermatology Clinic with a 4-month history of a bump on his left upper back. The lesion was tender and had been draining clear fluid and intermittent blood; he denied any preceding trauma. He had been seen both by his primary care physician and by a physician at an urgent care clinic, where he was told to use an antibiotic ointment and benzoyl peroxide daily on the area and advised to seek a dermatology consult should it not resolve. He did not see any improvement from these measures.

Physical exam revealed a 0.8-cm erythematous nodule with a peripheral collarette of scale at its base. The bandage used to cover the nodule was stained with hemorrhagic crust (FIGURE 1A). Superior and medial to the new lesion was a well-healed scar overlying much of the patient’s thoracic spine (FIGURE 1B).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Metastatic renal cell carcinoma

The nodule initially appeared to be a benign pyogenic granuloma. In fact, a biopsy of the nodule showed a profile similar to that of a pyogenic granuloma and it exhibited granulation tissue. However, further questioning revealed that the patient had a history of metastatic clear cell renal carcinoma. (The scar was from a prior unrelated orthopedic surgery.) Immunohistochemical stains showed positive staining in the cells of interest for PAX8 and CK8, 2 markers for renal cell lineage.

Consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy

Cutaneous metastasis to the skin is a rare event, representing roughly 2% of all skin tumors.¹ Anatomically, lesions tend to appear on the head and neck in men and anterior chest and abdomen in women.² Eruptions on the back, as seen in our patient, are relatively rare. The primary source of the metastasis also is gender dependent. Melanoma is the most common source overall; but in women, breast cancer represents the large majority of cutaneous metastases³ while in men lung, large intestine, and oral cavity tumors are the most common origin.³ Renal metastases are the fourth most common cause in men.³

The clinical morphology of cutaneous metastases is protean; the most common manifestations are nodules, papules, plaques, tumors, and ulcers.² Rare manifestations include alopecia plaques, erysipelas, herpes zoster–like eruptions,⁴ and pyogenic granuloma–like manifestations, as in our case. Pyogenic granuloma–like manifestations have been described in renal cell carcinoma, breast carcinoma, acute myelogenous leukemia,⁵ and hepatocellular carcinoma.⁶

Differential includes an array of erythematous nodules

The differential diagnosis of a lesion with the appearance of a pyogenic granuloma is ­variable.

Pyogenic granulomas tend to arise over a short period of time. They are more common in children and pregnant women. Pyogenic granulomas can manifest anywhere but often are reported on the digits and extremities. Clinical history is important to ensure no history of internal malignancy.

Continue to: Bartonella henselae

Bartonella henselae, known as “cat scratch disease,” also can present as a friable, erythematous nodule reminiscent of a pyogenic granuloma. Patients with bartonella henselae usually are immunocompromised and/or have had close contact with a cat.⁷

Kaposi sarcoma is a vascular tumor that may manifest as erythematous papules or nodules. Erythematous or violaceous patches or plaques may be present before a nodule arises. Kaposi sarcoma may manifest on the legs of elderly patients or anywhere on immunocompromised patients. Immunohistochemical stains for human herpesvirus-8 can clinch the diagnosis.⁸

Amelanotic melanoma may be impossible to discern clinically from a pyogenic granuloma. It appears as erythematous, violaceous, or flesh-colored nodules. Histologic evaluation is paramount in the diagnosis.⁹

Clinical suspicion should prompt a biopsy

The diagnosis of metastatic renal cell carcinoma is made on clinical suspicion and skin biopsy. Dermoscopy is an important tool in the evaluation of primary cutaneous tumors. Due to the rarity of cutaneous metastases, studies on dermoscopic findings in cutaneous metastases are limited to case series. One series showed a vascular dermoscopy pattern in 15 of 17 cases (88%).¹⁰

In light of this nonspecific pattern, it’s wise to consider biopsy of a pyogenic granuloma–like lesion or one with a vascular pattern on dermoscopy in any patient with a history of malignancy. Any lesion suspected of being a pyogenic granuloma that does not respond to conservative measures also would warrant a biopsy. Definitive diagnosis is made based upon histologic evaluation.

Continue to: Surgery is the cornerstone of treatment

 

 

Surgery is the cornerstone of treatment

Upon diagnosis, immediate referral for further local and systemic control is recommended. Treatment may consist of any combination of surgery, chemotherapy, immunotherapy, or radiation.¹¹

In this case, our patient was referred to Oncology for further treatment. Unfortunately, cutaneous metastases portend a very poor prognosis, with approximate survival times of 7.5 months.¹²

CORRESPONDENCE
M. Tye Haeberle, MD, 3810 Springhurst Boulevard, Ste 200, Louisville, KY 40241; tye.haeberle@gmail.com

The “heartbreak of psoriasis,” coined by an advertiser in the 1960s, conveyed the notion that this disease was a cosmetic disorder mainly limited to skin involvement. John Updike’s article in the September 1985 issue of The New Yorker, “At War With My Skin,” detailed Mr. Updike’s feelings of isolation and stress related to his condition, helping to reframe the popular concept of psoriasis.¹ Updike’s eloquent account describing his struggles to find effective treatment increased public awareness about psoriasis, which in fact affects other body systems as well.

The overall prevalence of psoriasis is 1.5% to 3.1% in the United States and United Kingdom.^2,3 More than 6.5 million adults in the United States > 20 years of age are affected.³ The most commonly affected demographic group is non-­Hispanic Caucasians.

Our expanding knowledge of pathogenesis

Studies of genetic linkage have identified genes and single nucleotide polymorphisms associated with psoriasis.⁴ The interaction between environmental triggers and the innate and adaptive immune systems leads to keratinocyte hyperproliferation. Tumor necrosis factor (TNF), interleukin (IL) 23, and IL-17 are important cytokines associated with psoriatic inflammation.⁴ There are common pathways of inflammation in both psoriasis and cardiovascular disease resulting in oxidative stress and endothelial cell dysfunction.⁴ Ninety percent of early-onset psoriasis is associated with human leukocyte antigen (HLA)-Cw6.⁴ And alterations in the microbiome of the skin may contribute, as reduced microbial diversity has been found in psoriatic lesions.⁵

Comorbidities are common

Psoriasis is an independent risk factor for diabetes and major adverse cardiovascular events.⁶ Hypertension, dyslipidemia, inflammatory bowel disease, nonalcoholic fatty liver disease, chronic kidney disease, and lymphoma (particularly cutaneous T-cell lymphoma) are also associated with psoriasis.⁶ Psoriatic arthritis is frequently encountered with cutaneous psoriasis; however, it is often not recognized until late in the disease course.

There also appears to be an association among psoriasis, dietary factors, and celiac disease.^7-9 Positive testing for IgA anti-endomysial antibodies and IgA tissue transglutaminase antibodies should prompt consideration of starting a gluten-free diet, which has been shown to improve psoriatic lesions.⁹ In addition to its impact on physical health, cutaneous psoriasis often affects mental health. Increased anxiety, depression, and sleep disorders are commonly encountered, revealing the far-reaching effects of psoriasis. The persistent associated itch of psoriasis is often distressing and negatively impacts the patient’s quality of life.

The different types of psoriasis

The classic presentation of psoriasis involves stubborn plaques with silvery scale on extensor surfaces such as the elbows and knees. The severity of the disease corresponds with the amount of body surface area affected. While plaque-type psoriasis is the most common form, other patterns exist. Individuals may exhibit 1 dominant pattern or multiple psoriatic variants simultaneously. Most types of psoriasis have 3 characteristic features: erythema, skin thickening, and scales.

Certain history and physical clues can aid in diagnosing psoriasis; these include the Koebner phenomenon, the Auspitz sign, and the Woronoff ring. The Koebner phenomenon refers to the development of psoriatic lesions in an area of trauma (FIGURE 1), frequently resulting in a linear streak-like appearance. The Auspitz sign describes the pinpoint bleeding that may be encountered with the removal of a psoriatic plaque. The Woronoff ring is a pale blanching ring that may surround a psoriatic lesion.

Continue to: Chronic plaque-type psoriasis

Chronic plaque-type psoriasis (Figures 2A and 2B), the most common variant, is characterized by sharply demarcated pink papules and plaques with a silvery scale in a symmetric distribution on the extensor surfaces, scalp, trunk, and lumbosacral areas.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Guttate psoriasis (FIGURE 3) features small (often < 1 cm) pink scaly papules that appear suddenly. It is more commonly seen in children and is usually preceded by an upper respiratory tract infection, often with Streptococcus.¹⁰ If strep testing is positive, guttate psoriasis may improve after appropriate antibiotic treatment.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Erythrodermic psoriasis (FIGUREs 4A and 4B) involves at least 75% of the body with erythema and scaling.¹¹ Erythroderma can be caused by many other conditions such as atopic dermatitis, a drug reaction, Sezary syndrome, seborrheic dermatitis, and pityriasis rubra pilaris. Treatments for other conditions in the differential diagnosis can potentially make psoriasis worse. Unfortunately, findings on a skin biopsy are often nonspecific, making careful clinical observation crucial to arriving at an accurate diagnosis.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Pustular psoriasis is characterized by bright erythema and sterile pustules. Pustular psoriasis can be triggered by pregnancy, sudden tapering of corticosteroids, hypocalcemia, and infection. Involvement of the palms and soles with severe desquamation can drastically impact daily functioning and quality of life.

Inverse or flexural psoriasis (FIGUREs 5A and 5B) is characterized by shiny, pink-to-red sharply demarcated plaques involving intertriginous areas, typically the groin, inguinal crease, axilla, inframammary regions, and intergluteal cleft.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Geographic tongue

Geographic tongue describes psoriasis of the tongue. The mucosa of the tongue has white plaques with a geographic border. Instead of scale, the moisture on the tongue causes areas of hyperkeratosis that appear white.

Nail psoriasis can manifest as nail pitting (FIGURE 6), oil staining, onycholysis (distal lifting of the nail), and subungual hyperkeratosis. Nail psoriasis is often quite distressing for patients and can be difficult to treat.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Palmoplantar psoriasis (FIGUREs 7A and 7B) can be painful due to the involvement of the palms of the hands and soles of the feet. Lesions will either be similar to other psoriatic plaques with well-demarcated erythematous scaling lesions or involve thickening and scale without associated erythema.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Psoriatic arthritis can cause significant joint damage and disability. Most affected individuals with psoriatic arthritis have a history of preceding skin disease.¹² There are no specific lab tests for psoriasis; radiologic studies can show bulky syndesmophytes, central and marginal erosions, and periostitis. Patterns of joint involvement are variable. Psoriatic arthritis is more likely to affect the distal interphalangeal joints than rheumatoid arthritis and is more likely to affect the metacarpophalangeal joints than osteoarthritis.¹³

Nail psoriasis is often quite distressing for patients and can be difficult to treat.

Psoriatic arthritis often progresses insidiously and is commonly described as causing discomfort rather than acute pain. Enthesitis, inflammation at the site where tendons or ligaments insert into the bone, is often present. Joint destruction may lead to the telescoping “opera glass” digit (FIGURE 8).

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Drug-provoked psoriasis

Drug-provoked psoriasis is divided into 2 groups: drug-induced and drug-­aggravated. Drug-induced psoriasis will improve after discontinuation of the causative drug and tends to occur in patients without a personal or family history of psoriasis. Drug-aggravated psoriasis continues to progress after the discontinuation of the offending drug and is more often seen in patients with a history of psoriasis.¹⁴ Drugs that most commonly provoke psoriasis are beta-blockers, lithium, and antimalarials.¹⁰ Other potentially aggravating agents include antibiotics, digoxin, and nonsteroidal anti-inflammatory drugs.¹⁰

Consider these skin disorders in the differential diagnosis

The diagnosis of psoriasis is usually clinical, and a skin biopsy is rarely needed. However, a range of other skin disorders should be kept in mind when considering the differential diagnosis.

Mycosis fungoides is a type of cutaneous T-cell lymphoma that forms erythematous plaques that may show wrinkling and epidermal atrophy in sun-protected sites. Onset usually occurs among the elderly.

Pityriasis rubra pilaris is characterized by salmon-colored patches that may have small areas of normal skin (“islands of sparing”), hyperkeratotic follicular papules, and hyperkeratosis of the palms and soles.

Seborrheic dermatitis, dandruff of the skin, usually involves the scalp and nasolabial areas and the T-zone of the face.

Continue to: Lichen planus

Lichen planus usually appears slightly more purple than psoriasis and typically involves the mouth, flexural surfaces of the wrists, genitals, and ankles.

Other conditions in the differential include pityriasis lichenoides chronica, which may be identified on skin biopsy. Inverse psoriasis can be difficult to differentiate from candida intertrigo, erythrasma, or tinea cruris.

A potassium hydroxide (KOH) preparation can help differentiate psoriasis from candida or tinea. In psoriasis, a KOH test will be negative for fungal elements. Mycology culture on skin scrapings may be performed to rule out fungal infection. Erythrasma may exhibit a coral red appearance under Wood lamp examination.

While plaque-type psoriasis is the most common form, other patterns exist and may even occur simultaneously

If a lesion fails to respond to appropriate treatment, a careful drug history and biopsy can help clarify the diagnosis.

Document disease

It’s important to thoroughly document the extent and severity of the psoriasis and to monitor the impact of treatment. The Psoriasis Area and Severity Index is a commonly used method that calculates a score based on the area (extent) of involvement surrounding 4 major anatomical regions (head, upper extremities, trunk, and lower extremities), as well as the degree of erythema, induration, and scaling of lesions. The average redness, thickness, and scaling are graded on a scale of 0 to 4 and the extent of involvement is calculated to form a total numerical score ranging from 0 (no disease) to 72 (maximal disease).

Continue to: Many options in the treatment arsenal

 

 

Many options in the treatment arsenal

Many treatments can improve psoriasis.^9,15-19 Most affected individuals discover that emollients and exposure to natural sunlight can be effective, as are soothing baths (balneotherapy) or topical coal tar application. More persistent disease requires prescription therapy. Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities (FIGURE 9).¹⁵

If ≤ 10% of the body surface area is involved, treatment options generally are explored in a stepwise progression from safest and most affordable to more involved therapies as needed: moisturization and avoidance of repetitive trauma, topical corticosteroids (TCS), vitamin D analogs, topical calcineurin inhibitors, and vitamin A creams. Recalcitrant disease will likely require ultraviolet (UV) light treatment or a systemic agent.¹⁵

If > 10% of the body surface area is involved, but joints are not involved, consider UV light treatment or a combination of alcitretin and TCS. If the joints are involved, likely initial options would be methotrexate, cyclosporine, or TNF-α inhibitor. Additional options to consider are anti-IL-17 or anti-IL-23 agents.¹⁵

If there’s joint involvement. In individuals with mild peripheral arthritis involving fewer than 4 joints without evidence of joint damage on imaging, nonsteroidal anti-inflammatory drugs are the mainstay of treatment. If the peripheral arthritis persists, or if it is associated with moderate-to-severe erosions or with substantial functional limitations, initiate treatment with a conventional disease-modifying antirheumatic drug. If the disease remains active, consider biologic agents.

Case studies

Mild-to-moderate psoriasis

Patient A is a 19-year-old woman presenting for evaluation of a persistently dry, flaking scalp. She has had the itchy scalp for years, as well as several small “patches” across her elbows, legs, knees, and abdomen. Over-the-counter emollients have not helped. The patient also says she has had brittle nails on several of her fingers, which she keeps covered with thick polish.

Continue to: The condition exemplified...

The condition exemplified by Patient A can typically be managed with topical products.

Topical steroids may be classified by different delivery vehicles, active ingredients, and potencies. The National Psoriasis Foundation's Topical Steroids Potency Chart can provide guidance (visit www.psoriasis.org/about-psoriasis/treatments/topicals/steroids/potency-chart and scroll down). Prescribing an appropriate amount is important; the standard 30-g prescription tube is generally required to cover the entire skin surface. Ointments have a greasy consistency (typically a petroleum base), which enhances potency and hydrates the skin. Creams and lotions are easier to rub on and spread. Gels are alcohol based and readily absorbed.¹⁶ Solutions, foams, and shampoos are particularly useful to treat psoriasis in hairy areas such as the scalp.

Corticosteroid potency ranges from Class I to Class VII, with the former being the most potent. While TCS products are typically effective with minimal systemic absorption, it is important to counsel patients on the risk of skin atrophy, impaired wound healing, and skin pigmentation changes with chronic use. With nail psoriasis, a potent topical steroid (including flurandrenolide [Cordran] tape) applied to the proximal nail fold has shown benefit.²⁰

Topical calcineurin inhibitors (TCIs; eg, tacrolimus ointment and pimecrolimus cream) are anti-inflammatory agents often used in conjunction with topical steroids to minimize steroid use and associated adverse effects.¹⁵ A possible steroid-sparing regimen includes using a TCI Monday through Friday and a topical steroid on the weekend.

Topical vitamin D analogs (calcipotriene, calcipotriol, calcitriol) inhibit proliferation of keratinocytes and decrease the production of inflammatory mediators.^15,17-19,21 Application of a vitamin D analog in combination with a high-potency TCS, systemic treatment, or phototherapy can provide greater efficacy, a more rapid onset of action, and less irritation than can the vitamin D analog used alone.²¹ If used in combination with UV light, apply topical vitamin D after the light therapy to prevent degradation.

Continue to: UV light therapy

UV light therapy is often used in ­cases refractory to topical therapy. Patients are typically prescribed 2 to 3 treatments per week with narrowband UVB (311-313 nm), the excimer laser (308 nm), or, less commonly, PUVA (UV treatment with psoralens). Treatment begins with a minimal erythema dose—the lowest dose to achieve minimal erythema of the skin before burning. When that is determined, exposure is increased as needed—depending on the response. If this is impractical or too time-consuming for the patient, an alternative recommendation would be increased exposure to natural sunlight or even use of a tanning booth. However, patients must then be cautioned about the increased risk of skin cancer.

Refractory/severe psoriasis

Patient B is a 35-year-old man with a longstanding history of psoriasis affecting his scalp and nails. Over the past 10 years, psoriatic lesions have also appeared and grown across his lower back, gluteal fold, legs, abdomen, and arms. He is now being evaluated by a rheumatologist for worsening symmetric joint pain that includes his lower back.

Methotrexate has been used to treat psoriasis and psoriatic arthritis since the 1950s. Methotrexate is a competitive inhibitor of dihydrofolate reductase and is typically given as an oral medication dosed once weekly with folic acid supplementation on the other 6 days.¹⁷ The most common adverse effects encountered with methotrexate are gastrointestinal upset and oral ulcers; however, routine monitoring for myelosuppression and hepatotoxicity is required.

Biologic therapy. When conventional therapies fail, immune-targeted treatment with “biologics” may be initiated. As knowledge of signaling pathways and the immunopathogenesis of psoriasis has increased, so has the number of biologic agents, which are generally well tolerated and effective in managing plaque psoriasis and psoriatic arthritis. Although their use, which requires monitoring, is handled primarily by specialists, familiarizing yourself with available agents can be helpful (TABLE).²²

Nutritional modification and supplementation in treating skin disease still requires further investigation. Fish oil has shown benefit for cutaneous psoriasis in randomized controlled trials.^7,8 Oral vitamin D supplementation requires further study, whereas selenium and B₁₂ supplementation have not conferred consistent benefit.⁷ Given that several studies have demonstrated a relationship between body mass index and psoriatic disease severity, weight loss may be helpful in the management of psoriasis as well as psoriatic arthritis.⁸

Continue to: Other systemic agents

Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities.

Other systemic agents—for individuals who cannot tolerate the biologic agents—include acitretin, azathioprine, mycophenolate mofetil, and cyclosporine.^15,17

Paradoxical psoriatic reactions

When a psoriatic condition develops during biologic drug therapy, it is known as a paradoxical psoriatic reaction. The onset of de novo psoriasis has been documented during TNF-α inhibitor therapy for individuals with underlying rheumatoid arthritis.²³ Skin biopsy reveals the same findings as common plaque psoriasis.

Using immunosuppressive Tx? Screen for tuberculosis

Testing to exclude a diagnosis of latent or undiagnosed tuberculosis must be performed prior to initiating immunosuppressive therapy with methotrexate or a biologic agent. Tuberculin skin testing, QuantiFERON-TB gold test, and the T-SPOT.TB test are accepted screening modalities. Discordance between tuberculin skin tests and the interferon gamma release assays in latent TB highlights the need for further study using the available QuantiFERON-TB gold test and the T-SPOT.TB test.²⁴

CORRESPONDENCE
Karl T. Clebak, MD, FAAFP, Penn State Health Milton S. Hershey Medical Center, Department of Family and Community Medicine, 500 University Drive, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu.

The “heartbreak of psoriasis,” coined by an advertiser in the 1960s, conveyed the notion that this disease was a cosmetic disorder mainly limited to skin involvement. John Updike’s article in the September 1985 issue of The New Yorker, “At War With My Skin,” detailed Mr. Updike’s feelings of isolation and stress related to his condition, helping to reframe the popular concept of psoriasis.¹ Updike’s eloquent account describing his struggles to find effective treatment increased public awareness about psoriasis, which in fact affects other body systems as well.

The overall prevalence of psoriasis is 1.5% to 3.1% in the United States and United Kingdom.^2,3 More than 6.5 million adults in the United States > 20 years of age are affected.³ The most commonly affected demographic group is non-­Hispanic Caucasians.

Our expanding knowledge of pathogenesis

Studies of genetic linkage have identified genes and single nucleotide polymorphisms associated with psoriasis.⁴ The interaction between environmental triggers and the innate and adaptive immune systems leads to keratinocyte hyperproliferation. Tumor necrosis factor (TNF), interleukin (IL) 23, and IL-17 are important cytokines associated with psoriatic inflammation.⁴ There are common pathways of inflammation in both psoriasis and cardiovascular disease resulting in oxidative stress and endothelial cell dysfunction.⁴ Ninety percent of early-onset psoriasis is associated with human leukocyte antigen (HLA)-Cw6.⁴ And alterations in the microbiome of the skin may contribute, as reduced microbial diversity has been found in psoriatic lesions.⁵

Comorbidities are common

Psoriasis is an independent risk factor for diabetes and major adverse cardiovascular events.⁶ Hypertension, dyslipidemia, inflammatory bowel disease, nonalcoholic fatty liver disease, chronic kidney disease, and lymphoma (particularly cutaneous T-cell lymphoma) are also associated with psoriasis.⁶ Psoriatic arthritis is frequently encountered with cutaneous psoriasis; however, it is often not recognized until late in the disease course.

There also appears to be an association among psoriasis, dietary factors, and celiac disease.^7-9 Positive testing for IgA anti-endomysial antibodies and IgA tissue transglutaminase antibodies should prompt consideration of starting a gluten-free diet, which has been shown to improve psoriatic lesions.⁹ In addition to its impact on physical health, cutaneous psoriasis often affects mental health. Increased anxiety, depression, and sleep disorders are commonly encountered, revealing the far-reaching effects of psoriasis. The persistent associated itch of psoriasis is often distressing and negatively impacts the patient’s quality of life.

The different types of psoriasis

The classic presentation of psoriasis involves stubborn plaques with silvery scale on extensor surfaces such as the elbows and knees. The severity of the disease corresponds with the amount of body surface area affected. While plaque-type psoriasis is the most common form, other patterns exist. Individuals may exhibit 1 dominant pattern or multiple psoriatic variants simultaneously. Most types of psoriasis have 3 characteristic features: erythema, skin thickening, and scales.

Certain history and physical clues can aid in diagnosing psoriasis; these include the Koebner phenomenon, the Auspitz sign, and the Woronoff ring. The Koebner phenomenon refers to the development of psoriatic lesions in an area of trauma (FIGURE 1), frequently resulting in a linear streak-like appearance. The Auspitz sign describes the pinpoint bleeding that may be encountered with the removal of a psoriatic plaque. The Woronoff ring is a pale blanching ring that may surround a psoriatic lesion.

Continue to: Chronic plaque-type psoriasis

Chronic plaque-type psoriasis (Figures 2A and 2B), the most common variant, is characterized by sharply demarcated pink papules and plaques with a silvery scale in a symmetric distribution on the extensor surfaces, scalp, trunk, and lumbosacral areas.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Guttate psoriasis (FIGURE 3) features small (often < 1 cm) pink scaly papules that appear suddenly. It is more commonly seen in children and is usually preceded by an upper respiratory tract infection, often with Streptococcus.¹⁰ If strep testing is positive, guttate psoriasis may improve after appropriate antibiotic treatment.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Erythrodermic psoriasis (FIGUREs 4A and 4B) involves at least 75% of the body with erythema and scaling.¹¹ Erythroderma can be caused by many other conditions such as atopic dermatitis, a drug reaction, Sezary syndrome, seborrheic dermatitis, and pityriasis rubra pilaris. Treatments for other conditions in the differential diagnosis can potentially make psoriasis worse. Unfortunately, findings on a skin biopsy are often nonspecific, making careful clinical observation crucial to arriving at an accurate diagnosis.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Pustular psoriasis is characterized by bright erythema and sterile pustules. Pustular psoriasis can be triggered by pregnancy, sudden tapering of corticosteroids, hypocalcemia, and infection. Involvement of the palms and soles with severe desquamation can drastically impact daily functioning and quality of life.

Inverse or flexural psoriasis (FIGUREs 5A and 5B) is characterized by shiny, pink-to-red sharply demarcated plaques involving intertriginous areas, typically the groin, inguinal crease, axilla, inframammary regions, and intergluteal cleft.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Geographic tongue

Geographic tongue describes psoriasis of the tongue. The mucosa of the tongue has white plaques with a geographic border. Instead of scale, the moisture on the tongue causes areas of hyperkeratosis that appear white.

Nail psoriasis can manifest as nail pitting (FIGURE 6), oil staining, onycholysis (distal lifting of the nail), and subungual hyperkeratosis. Nail psoriasis is often quite distressing for patients and can be difficult to treat.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Palmoplantar psoriasis (FIGUREs 7A and 7B) can be painful due to the involvement of the palms of the hands and soles of the feet. Lesions will either be similar to other psoriatic plaques with well-demarcated erythematous scaling lesions or involve thickening and scale without associated erythema.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Psoriatic arthritis can cause significant joint damage and disability. Most affected individuals with psoriatic arthritis have a history of preceding skin disease.¹² There are no specific lab tests for psoriasis; radiologic studies can show bulky syndesmophytes, central and marginal erosions, and periostitis. Patterns of joint involvement are variable. Psoriatic arthritis is more likely to affect the distal interphalangeal joints than rheumatoid arthritis and is more likely to affect the metacarpophalangeal joints than osteoarthritis.¹³

Nail psoriasis is often quite distressing for patients and can be difficult to treat.

Psoriatic arthritis often progresses insidiously and is commonly described as causing discomfort rather than acute pain. Enthesitis, inflammation at the site where tendons or ligaments insert into the bone, is often present. Joint destruction may lead to the telescoping “opera glass” digit (FIGURE 8).

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Drug-provoked psoriasis

Drug-provoked psoriasis is divided into 2 groups: drug-induced and drug-­aggravated. Drug-induced psoriasis will improve after discontinuation of the causative drug and tends to occur in patients without a personal or family history of psoriasis. Drug-aggravated psoriasis continues to progress after the discontinuation of the offending drug and is more often seen in patients with a history of psoriasis.¹⁴ Drugs that most commonly provoke psoriasis are beta-blockers, lithium, and antimalarials.¹⁰ Other potentially aggravating agents include antibiotics, digoxin, and nonsteroidal anti-inflammatory drugs.¹⁰

Consider these skin disorders in the differential diagnosis

The diagnosis of psoriasis is usually clinical, and a skin biopsy is rarely needed. However, a range of other skin disorders should be kept in mind when considering the differential diagnosis.

Mycosis fungoides is a type of cutaneous T-cell lymphoma that forms erythematous plaques that may show wrinkling and epidermal atrophy in sun-protected sites. Onset usually occurs among the elderly.

Pityriasis rubra pilaris is characterized by salmon-colored patches that may have small areas of normal skin (“islands of sparing”), hyperkeratotic follicular papules, and hyperkeratosis of the palms and soles.

Seborrheic dermatitis, dandruff of the skin, usually involves the scalp and nasolabial areas and the T-zone of the face.

Continue to: Lichen planus

Lichen planus usually appears slightly more purple than psoriasis and typically involves the mouth, flexural surfaces of the wrists, genitals, and ankles.

Other conditions in the differential include pityriasis lichenoides chronica, which may be identified on skin biopsy. Inverse psoriasis can be difficult to differentiate from candida intertrigo, erythrasma, or tinea cruris.

A potassium hydroxide (KOH) preparation can help differentiate psoriasis from candida or tinea. In psoriasis, a KOH test will be negative for fungal elements. Mycology culture on skin scrapings may be performed to rule out fungal infection. Erythrasma may exhibit a coral red appearance under Wood lamp examination.

While plaque-type psoriasis is the most common form, other patterns exist and may even occur simultaneously

If a lesion fails to respond to appropriate treatment, a careful drug history and biopsy can help clarify the diagnosis.

Document disease

It’s important to thoroughly document the extent and severity of the psoriasis and to monitor the impact of treatment. The Psoriasis Area and Severity Index is a commonly used method that calculates a score based on the area (extent) of involvement surrounding 4 major anatomical regions (head, upper extremities, trunk, and lower extremities), as well as the degree of erythema, induration, and scaling of lesions. The average redness, thickness, and scaling are graded on a scale of 0 to 4 and the extent of involvement is calculated to form a total numerical score ranging from 0 (no disease) to 72 (maximal disease).

Continue to: Many options in the treatment arsenal

 

 

Many options in the treatment arsenal

Many treatments can improve psoriasis.^9,15-19 Most affected individuals discover that emollients and exposure to natural sunlight can be effective, as are soothing baths (balneotherapy) or topical coal tar application. More persistent disease requires prescription therapy. Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities (FIGURE 9).¹⁵

If ≤ 10% of the body surface area is involved, treatment options generally are explored in a stepwise progression from safest and most affordable to more involved therapies as needed: moisturization and avoidance of repetitive trauma, topical corticosteroids (TCS), vitamin D analogs, topical calcineurin inhibitors, and vitamin A creams. Recalcitrant disease will likely require ultraviolet (UV) light treatment or a systemic agent.¹⁵

If > 10% of the body surface area is involved, but joints are not involved, consider UV light treatment or a combination of alcitretin and TCS. If the joints are involved, likely initial options would be methotrexate, cyclosporine, or TNF-α inhibitor. Additional options to consider are anti-IL-17 or anti-IL-23 agents.¹⁵

If there’s joint involvement. In individuals with mild peripheral arthritis involving fewer than 4 joints without evidence of joint damage on imaging, nonsteroidal anti-inflammatory drugs are the mainstay of treatment. If the peripheral arthritis persists, or if it is associated with moderate-to-severe erosions or with substantial functional limitations, initiate treatment with a conventional disease-modifying antirheumatic drug. If the disease remains active, consider biologic agents.

Case studies

Mild-to-moderate psoriasis

Patient A is a 19-year-old woman presenting for evaluation of a persistently dry, flaking scalp. She has had the itchy scalp for years, as well as several small “patches” across her elbows, legs, knees, and abdomen. Over-the-counter emollients have not helped. The patient also says she has had brittle nails on several of her fingers, which she keeps covered with thick polish.

Continue to: The condition exemplified...

The condition exemplified by Patient A can typically be managed with topical products.

Topical steroids may be classified by different delivery vehicles, active ingredients, and potencies. The National Psoriasis Foundation's Topical Steroids Potency Chart can provide guidance (visit www.psoriasis.org/about-psoriasis/treatments/topicals/steroids/potency-chart and scroll down). Prescribing an appropriate amount is important; the standard 30-g prescription tube is generally required to cover the entire skin surface. Ointments have a greasy consistency (typically a petroleum base), which enhances potency and hydrates the skin. Creams and lotions are easier to rub on and spread. Gels are alcohol based and readily absorbed.¹⁶ Solutions, foams, and shampoos are particularly useful to treat psoriasis in hairy areas such as the scalp.

Corticosteroid potency ranges from Class I to Class VII, with the former being the most potent. While TCS products are typically effective with minimal systemic absorption, it is important to counsel patients on the risk of skin atrophy, impaired wound healing, and skin pigmentation changes with chronic use. With nail psoriasis, a potent topical steroid (including flurandrenolide [Cordran] tape) applied to the proximal nail fold has shown benefit.²⁰

Topical calcineurin inhibitors (TCIs; eg, tacrolimus ointment and pimecrolimus cream) are anti-inflammatory agents often used in conjunction with topical steroids to minimize steroid use and associated adverse effects.¹⁵ A possible steroid-sparing regimen includes using a TCI Monday through Friday and a topical steroid on the weekend.

Topical vitamin D analogs (calcipotriene, calcipotriol, calcitriol) inhibit proliferation of keratinocytes and decrease the production of inflammatory mediators.^15,17-19,21 Application of a vitamin D analog in combination with a high-potency TCS, systemic treatment, or phototherapy can provide greater efficacy, a more rapid onset of action, and less irritation than can the vitamin D analog used alone.²¹ If used in combination with UV light, apply topical vitamin D after the light therapy to prevent degradation.

Continue to: UV light therapy

UV light therapy is often used in ­cases refractory to topical therapy. Patients are typically prescribed 2 to 3 treatments per week with narrowband UVB (311-313 nm), the excimer laser (308 nm), or, less commonly, PUVA (UV treatment with psoralens). Treatment begins with a minimal erythema dose—the lowest dose to achieve minimal erythema of the skin before burning. When that is determined, exposure is increased as needed—depending on the response. If this is impractical or too time-consuming for the patient, an alternative recommendation would be increased exposure to natural sunlight or even use of a tanning booth. However, patients must then be cautioned about the increased risk of skin cancer.

Refractory/severe psoriasis

Patient B is a 35-year-old man with a longstanding history of psoriasis affecting his scalp and nails. Over the past 10 years, psoriatic lesions have also appeared and grown across his lower back, gluteal fold, legs, abdomen, and arms. He is now being evaluated by a rheumatologist for worsening symmetric joint pain that includes his lower back.

Methotrexate has been used to treat psoriasis and psoriatic arthritis since the 1950s. Methotrexate is a competitive inhibitor of dihydrofolate reductase and is typically given as an oral medication dosed once weekly with folic acid supplementation on the other 6 days.¹⁷ The most common adverse effects encountered with methotrexate are gastrointestinal upset and oral ulcers; however, routine monitoring for myelosuppression and hepatotoxicity is required.

Biologic therapy. When conventional therapies fail, immune-targeted treatment with “biologics” may be initiated. As knowledge of signaling pathways and the immunopathogenesis of psoriasis has increased, so has the number of biologic agents, which are generally well tolerated and effective in managing plaque psoriasis and psoriatic arthritis. Although their use, which requires monitoring, is handled primarily by specialists, familiarizing yourself with available agents can be helpful (TABLE).²²

Nutritional modification and supplementation in treating skin disease still requires further investigation. Fish oil has shown benefit for cutaneous psoriasis in randomized controlled trials.^7,8 Oral vitamin D supplementation requires further study, whereas selenium and B₁₂ supplementation have not conferred consistent benefit.⁷ Given that several studies have demonstrated a relationship between body mass index and psoriatic disease severity, weight loss may be helpful in the management of psoriasis as well as psoriatic arthritis.⁸

Continue to: Other systemic agents

Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities.

Other systemic agents—for individuals who cannot tolerate the biologic agents—include acitretin, azathioprine, mycophenolate mofetil, and cyclosporine.^15,17

Paradoxical psoriatic reactions

When a psoriatic condition develops during biologic drug therapy, it is known as a paradoxical psoriatic reaction. The onset of de novo psoriasis has been documented during TNF-α inhibitor therapy for individuals with underlying rheumatoid arthritis.²³ Skin biopsy reveals the same findings as common plaque psoriasis.

Using immunosuppressive Tx? Screen for tuberculosis

Testing to exclude a diagnosis of latent or undiagnosed tuberculosis must be performed prior to initiating immunosuppressive therapy with methotrexate or a biologic agent. Tuberculin skin testing, QuantiFERON-TB gold test, and the T-SPOT.TB test are accepted screening modalities. Discordance between tuberculin skin tests and the interferon gamma release assays in latent TB highlights the need for further study using the available QuantiFERON-TB gold test and the T-SPOT.TB test.²⁴

CORRESPONDENCE
Karl T. Clebak, MD, FAAFP, Penn State Health Milton S. Hershey Medical Center, Department of Family and Community Medicine, 500 University Drive, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu.

The “heartbreak of psoriasis,” coined by an advertiser in the 1960s, conveyed the notion that this disease was a cosmetic disorder mainly limited to skin involvement. John Updike’s article in the September 1985 issue of The New Yorker, “At War With My Skin,” detailed Mr. Updike’s feelings of isolation and stress related to his condition, helping to reframe the popular concept of psoriasis.¹ Updike’s eloquent account describing his struggles to find effective treatment increased public awareness about psoriasis, which in fact affects other body systems as well.

The overall prevalence of psoriasis is 1.5% to 3.1% in the United States and United Kingdom.^2,3 More than 6.5 million adults in the United States > 20 years of age are affected.³ The most commonly affected demographic group is non-­Hispanic Caucasians.

Our expanding knowledge of pathogenesis

Studies of genetic linkage have identified genes and single nucleotide polymorphisms associated with psoriasis.⁴ The interaction between environmental triggers and the innate and adaptive immune systems leads to keratinocyte hyperproliferation. Tumor necrosis factor (TNF), interleukin (IL) 23, and IL-17 are important cytokines associated with psoriatic inflammation.⁴ There are common pathways of inflammation in both psoriasis and cardiovascular disease resulting in oxidative stress and endothelial cell dysfunction.⁴ Ninety percent of early-onset psoriasis is associated with human leukocyte antigen (HLA)-Cw6.⁴ And alterations in the microbiome of the skin may contribute, as reduced microbial diversity has been found in psoriatic lesions.⁵

Comorbidities are common

Psoriasis is an independent risk factor for diabetes and major adverse cardiovascular events.⁶ Hypertension, dyslipidemia, inflammatory bowel disease, nonalcoholic fatty liver disease, chronic kidney disease, and lymphoma (particularly cutaneous T-cell lymphoma) are also associated with psoriasis.⁶ Psoriatic arthritis is frequently encountered with cutaneous psoriasis; however, it is often not recognized until late in the disease course.

There also appears to be an association among psoriasis, dietary factors, and celiac disease.^7-9 Positive testing for IgA anti-endomysial antibodies and IgA tissue transglutaminase antibodies should prompt consideration of starting a gluten-free diet, which has been shown to improve psoriatic lesions.⁹ In addition to its impact on physical health, cutaneous psoriasis often affects mental health. Increased anxiety, depression, and sleep disorders are commonly encountered, revealing the far-reaching effects of psoriasis. The persistent associated itch of psoriasis is often distressing and negatively impacts the patient’s quality of life.

The different types of psoriasis

The classic presentation of psoriasis involves stubborn plaques with silvery scale on extensor surfaces such as the elbows and knees. The severity of the disease corresponds with the amount of body surface area affected. While plaque-type psoriasis is the most common form, other patterns exist. Individuals may exhibit 1 dominant pattern or multiple psoriatic variants simultaneously. Most types of psoriasis have 3 characteristic features: erythema, skin thickening, and scales.

Certain history and physical clues can aid in diagnosing psoriasis; these include the Koebner phenomenon, the Auspitz sign, and the Woronoff ring. The Koebner phenomenon refers to the development of psoriatic lesions in an area of trauma (FIGURE 1), frequently resulting in a linear streak-like appearance. The Auspitz sign describes the pinpoint bleeding that may be encountered with the removal of a psoriatic plaque. The Woronoff ring is a pale blanching ring that may surround a psoriatic lesion.

Continue to: Chronic plaque-type psoriasis

Chronic plaque-type psoriasis (Figures 2A and 2B), the most common variant, is characterized by sharply demarcated pink papules and plaques with a silvery scale in a symmetric distribution on the extensor surfaces, scalp, trunk, and lumbosacral areas.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Guttate psoriasis (FIGURE 3) features small (often < 1 cm) pink scaly papules that appear suddenly. It is more commonly seen in children and is usually preceded by an upper respiratory tract infection, often with Streptococcus.¹⁰ If strep testing is positive, guttate psoriasis may improve after appropriate antibiotic treatment.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Erythrodermic psoriasis (FIGUREs 4A and 4B) involves at least 75% of the body with erythema and scaling.¹¹ Erythroderma can be caused by many other conditions such as atopic dermatitis, a drug reaction, Sezary syndrome, seborrheic dermatitis, and pityriasis rubra pilaris. Treatments for other conditions in the differential diagnosis can potentially make psoriasis worse. Unfortunately, findings on a skin biopsy are often nonspecific, making careful clinical observation crucial to arriving at an accurate diagnosis.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Pustular psoriasis is characterized by bright erythema and sterile pustules. Pustular psoriasis can be triggered by pregnancy, sudden tapering of corticosteroids, hypocalcemia, and infection. Involvement of the palms and soles with severe desquamation can drastically impact daily functioning and quality of life.

Inverse or flexural psoriasis (FIGUREs 5A and 5B) is characterized by shiny, pink-to-red sharply demarcated plaques involving intertriginous areas, typically the groin, inguinal crease, axilla, inframammary regions, and intergluteal cleft.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Geographic tongue

Geographic tongue describes psoriasis of the tongue. The mucosa of the tongue has white plaques with a geographic border. Instead of scale, the moisture on the tongue causes areas of hyperkeratosis that appear white.

Nail psoriasis can manifest as nail pitting (FIGURE 6), oil staining, onycholysis (distal lifting of the nail), and subungual hyperkeratosis. Nail psoriasis is often quite distressing for patients and can be difficult to treat.

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Palmoplantar psoriasis (FIGUREs 7A and 7B) can be painful due to the involvement of the palms of the hands and soles of the feet. Lesions will either be similar to other psoriatic plaques with well-demarcated erythematous scaling lesions or involve thickening and scale without associated erythema.

PHOTOS COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Psoriatic arthritis can cause significant joint damage and disability. Most affected individuals with psoriatic arthritis have a history of preceding skin disease.¹² There are no specific lab tests for psoriasis; radiologic studies can show bulky syndesmophytes, central and marginal erosions, and periostitis. Patterns of joint involvement are variable. Psoriatic arthritis is more likely to affect the distal interphalangeal joints than rheumatoid arthritis and is more likely to affect the metacarpophalangeal joints than osteoarthritis.¹³

Nail psoriasis is often quite distressing for patients and can be difficult to treat.

Psoriatic arthritis often progresses insidiously and is commonly described as causing discomfort rather than acute pain. Enthesitis, inflammation at the site where tendons or ligaments insert into the bone, is often present. Joint destruction may lead to the telescoping “opera glass” digit (FIGURE 8).

PHOTO COURTESY OF JEFFREY J. MILLER, MD, MBA, PENN STATE COLLEGE OF MEDICINE, AND BRYAN E. ANDERSON, MD, PENN STATE COLLEGE OF MEDICINE, DEPARTMENT OF DERMATOLOGY, PA

Continue to: Drug-provoked psoriasis

Drug-provoked psoriasis is divided into 2 groups: drug-induced and drug-­aggravated. Drug-induced psoriasis will improve after discontinuation of the causative drug and tends to occur in patients without a personal or family history of psoriasis. Drug-aggravated psoriasis continues to progress after the discontinuation of the offending drug and is more often seen in patients with a history of psoriasis.¹⁴ Drugs that most commonly provoke psoriasis are beta-blockers, lithium, and antimalarials.¹⁰ Other potentially aggravating agents include antibiotics, digoxin, and nonsteroidal anti-inflammatory drugs.¹⁰

Consider these skin disorders in the differential diagnosis

The diagnosis of psoriasis is usually clinical, and a skin biopsy is rarely needed. However, a range of other skin disorders should be kept in mind when considering the differential diagnosis.

Mycosis fungoides is a type of cutaneous T-cell lymphoma that forms erythematous plaques that may show wrinkling and epidermal atrophy in sun-protected sites. Onset usually occurs among the elderly.

Pityriasis rubra pilaris is characterized by salmon-colored patches that may have small areas of normal skin (“islands of sparing”), hyperkeratotic follicular papules, and hyperkeratosis of the palms and soles.

Seborrheic dermatitis, dandruff of the skin, usually involves the scalp and nasolabial areas and the T-zone of the face.

Continue to: Lichen planus

Lichen planus usually appears slightly more purple than psoriasis and typically involves the mouth, flexural surfaces of the wrists, genitals, and ankles.

Other conditions in the differential include pityriasis lichenoides chronica, which may be identified on skin biopsy. Inverse psoriasis can be difficult to differentiate from candida intertrigo, erythrasma, or tinea cruris.

A potassium hydroxide (KOH) preparation can help differentiate psoriasis from candida or tinea. In psoriasis, a KOH test will be negative for fungal elements. Mycology culture on skin scrapings may be performed to rule out fungal infection. Erythrasma may exhibit a coral red appearance under Wood lamp examination.

While plaque-type psoriasis is the most common form, other patterns exist and may even occur simultaneously

If a lesion fails to respond to appropriate treatment, a careful drug history and biopsy can help clarify the diagnosis.

Document disease

It’s important to thoroughly document the extent and severity of the psoriasis and to monitor the impact of treatment. The Psoriasis Area and Severity Index is a commonly used method that calculates a score based on the area (extent) of involvement surrounding 4 major anatomical regions (head, upper extremities, trunk, and lower extremities), as well as the degree of erythema, induration, and scaling of lesions. The average redness, thickness, and scaling are graded on a scale of 0 to 4 and the extent of involvement is calculated to form a total numerical score ranging from 0 (no disease) to 72 (maximal disease).

Continue to: Many options in the treatment arsenal

 

 

Many options in the treatment arsenal

Many treatments can improve psoriasis.^9,15-19 Most affected individuals discover that emollients and exposure to natural sunlight can be effective, as are soothing baths (balneotherapy) or topical coal tar application. More persistent disease requires prescription therapy. Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities (FIGURE 9).¹⁵

If ≤ 10% of the body surface area is involved, treatment options generally are explored in a stepwise progression from safest and most affordable to more involved therapies as needed: moisturization and avoidance of repetitive trauma, topical corticosteroids (TCS), vitamin D analogs, topical calcineurin inhibitors, and vitamin A creams. Recalcitrant disease will likely require ultraviolet (UV) light treatment or a systemic agent.¹⁵

If > 10% of the body surface area is involved, but joints are not involved, consider UV light treatment or a combination of alcitretin and TCS. If the joints are involved, likely initial options would be methotrexate, cyclosporine, or TNF-α inhibitor. Additional options to consider are anti-IL-17 or anti-IL-23 agents.¹⁵

If there’s joint involvement. In individuals with mild peripheral arthritis involving fewer than 4 joints without evidence of joint damage on imaging, nonsteroidal anti-inflammatory drugs are the mainstay of treatment. If the peripheral arthritis persists, or if it is associated with moderate-to-severe erosions or with substantial functional limitations, initiate treatment with a conventional disease-modifying antirheumatic drug. If the disease remains active, consider biologic agents.

Case studies

Mild-to-moderate psoriasis

Patient A is a 19-year-old woman presenting for evaluation of a persistently dry, flaking scalp. She has had the itchy scalp for years, as well as several small “patches” across her elbows, legs, knees, and abdomen. Over-the-counter emollients have not helped. The patient also says she has had brittle nails on several of her fingers, which she keeps covered with thick polish.

Continue to: The condition exemplified...

The condition exemplified by Patient A can typically be managed with topical products.

Topical steroids may be classified by different delivery vehicles, active ingredients, and potencies. The National Psoriasis Foundation's Topical Steroids Potency Chart can provide guidance (visit www.psoriasis.org/about-psoriasis/treatments/topicals/steroids/potency-chart and scroll down). Prescribing an appropriate amount is important; the standard 30-g prescription tube is generally required to cover the entire skin surface. Ointments have a greasy consistency (typically a petroleum base), which enhances potency and hydrates the skin. Creams and lotions are easier to rub on and spread. Gels are alcohol based and readily absorbed.¹⁶ Solutions, foams, and shampoos are particularly useful to treat psoriasis in hairy areas such as the scalp.

Corticosteroid potency ranges from Class I to Class VII, with the former being the most potent. While TCS products are typically effective with minimal systemic absorption, it is important to counsel patients on the risk of skin atrophy, impaired wound healing, and skin pigmentation changes with chronic use. With nail psoriasis, a potent topical steroid (including flurandrenolide [Cordran] tape) applied to the proximal nail fold has shown benefit.²⁰

Topical calcineurin inhibitors (TCIs; eg, tacrolimus ointment and pimecrolimus cream) are anti-inflammatory agents often used in conjunction with topical steroids to minimize steroid use and associated adverse effects.¹⁵ A possible steroid-sparing regimen includes using a TCI Monday through Friday and a topical steroid on the weekend.

Topical vitamin D analogs (calcipotriene, calcipotriol, calcitriol) inhibit proliferation of keratinocytes and decrease the production of inflammatory mediators.^15,17-19,21 Application of a vitamin D analog in combination with a high-potency TCS, systemic treatment, or phototherapy can provide greater efficacy, a more rapid onset of action, and less irritation than can the vitamin D analog used alone.²¹ If used in combination with UV light, apply topical vitamin D after the light therapy to prevent degradation.

Continue to: UV light therapy

UV light therapy is often used in ­cases refractory to topical therapy. Patients are typically prescribed 2 to 3 treatments per week with narrowband UVB (311-313 nm), the excimer laser (308 nm), or, less commonly, PUVA (UV treatment with psoralens). Treatment begins with a minimal erythema dose—the lowest dose to achieve minimal erythema of the skin before burning. When that is determined, exposure is increased as needed—depending on the response. If this is impractical or too time-consuming for the patient, an alternative recommendation would be increased exposure to natural sunlight or even use of a tanning booth. However, patients must then be cautioned about the increased risk of skin cancer.

Refractory/severe psoriasis

Patient B is a 35-year-old man with a longstanding history of psoriasis affecting his scalp and nails. Over the past 10 years, psoriatic lesions have also appeared and grown across his lower back, gluteal fold, legs, abdomen, and arms. He is now being evaluated by a rheumatologist for worsening symmetric joint pain that includes his lower back.

Methotrexate has been used to treat psoriasis and psoriatic arthritis since the 1950s. Methotrexate is a competitive inhibitor of dihydrofolate reductase and is typically given as an oral medication dosed once weekly with folic acid supplementation on the other 6 days.¹⁷ The most common adverse effects encountered with methotrexate are gastrointestinal upset and oral ulcers; however, routine monitoring for myelosuppression and hepatotoxicity is required.

Biologic therapy. When conventional therapies fail, immune-targeted treatment with “biologics” may be initiated. As knowledge of signaling pathways and the immunopathogenesis of psoriasis has increased, so has the number of biologic agents, which are generally well tolerated and effective in managing plaque psoriasis and psoriatic arthritis. Although their use, which requires monitoring, is handled primarily by specialists, familiarizing yourself with available agents can be helpful (TABLE).²²

Nutritional modification and supplementation in treating skin disease still requires further investigation. Fish oil has shown benefit for cutaneous psoriasis in randomized controlled trials.^7,8 Oral vitamin D supplementation requires further study, whereas selenium and B₁₂ supplementation have not conferred consistent benefit.⁷ Given that several studies have demonstrated a relationship between body mass index and psoriatic disease severity, weight loss may be helpful in the management of psoriasis as well as psoriatic arthritis.⁸

Continue to: Other systemic agents

Individualize therapy according to the severity of disease, location of the lesions, involvement of joints, and comorbidities.

Other systemic agents—for individuals who cannot tolerate the biologic agents—include acitretin, azathioprine, mycophenolate mofetil, and cyclosporine.^15,17

Paradoxical psoriatic reactions

When a psoriatic condition develops during biologic drug therapy, it is known as a paradoxical psoriatic reaction. The onset of de novo psoriasis has been documented during TNF-α inhibitor therapy for individuals with underlying rheumatoid arthritis.²³ Skin biopsy reveals the same findings as common plaque psoriasis.

Using immunosuppressive Tx? Screen for tuberculosis

Testing to exclude a diagnosis of latent or undiagnosed tuberculosis must be performed prior to initiating immunosuppressive therapy with methotrexate or a biologic agent. Tuberculin skin testing, QuantiFERON-TB gold test, and the T-SPOT.TB test are accepted screening modalities. Discordance between tuberculin skin tests and the interferon gamma release assays in latent TB highlights the need for further study using the available QuantiFERON-TB gold test and the T-SPOT.TB test.²⁴

CORRESPONDENCE
Karl T. Clebak, MD, FAAFP, Penn State Health Milton S. Hershey Medical Center, Department of Family and Community Medicine, 500 University Drive, Hershey, PA 17033; kclebak@pennstatehealth.psu.edu.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Based on the clinical appearance of hyperpigmented and hypopigmented scaly plaques in sun-exposed facial areas (with associated scarring and follicular plugging in affected lesions), the patient was given a diagnosis of discoid lupus erythematosus. The diagnosis was confirmed with a punch biopsy that showed characteristic interface dermatitis with superficial and deep perivascular and peri-adnexal lymphocytes. Direct immunofluorescence showed a band of C3 at the dermo-epidermal junction, consistent with various forms of cutaneous lupus.

A review of systems was negative for signs of systemic disease, including a lack of weakness, joint pain/swelling, fever, or known blood clots. An antinuclear antibody panel was also negative, largely excluding systemic disease.

Discoid lupus erythematosus is a form of cutaneous lupus. Patients often are genetically predisposed to autoimmune disease, and disease may be triggered by sun exposure. Up to 80% of patients develop lesions that are limited to the head and neck. Up to 25% of patients develop systemic lupus erythematosus that may occur months—or even decades—after the initial diagnosis. Lesions may lead to longstanding scars; this cannot always be prevented.

Two- to 3-week trials of topical potent or superpotent steroids applied to affected plaques may lead to clearance. Additionally, lesions may be treated with intralesional triamcinolone 3 mg/mL to 10 mg/mL and repeated every 3 to 4 weeks. Systemic therapies include hydroxychloroquine, chloroquine, retinoids, steroid sparing immunomodulators, and rarely prednisone.

This patient tolerated topical therapy well and though some scars remained, he was able to control flares with 2- to 3-week courses of clobetasol 0.05% twice daily. He is followed 2 to 3 times annually and has not developed signs or serologic findings of systemic disease over several years.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

In a survey of products labeled as hypoallergenic for children, about half of shampoos and almost 44% of soaps contained cocamidopropyl betaine (CAPB), a suspected sensitizer for hypersensitivity reactions in people with atopic dermatitis (AD) and allergic contact dermatitis, according to a research letter in the Journal of the American Academy of Dermatology.

Pirotehnik/iStock/Getty Images

In the letter, the authors, Reid W. Collis, of Washington University in St. Louis, and David M. Sheinbein, MD, of the division of dermatology at the university, referred to a previous study showing an association between contact sensitivity with CAPB and people with a history of AD. This was supported by the results of their own recent study in pediatric patients, they wrote, which found that reactions to CAPB were “exclusively” in patients with AD.

In the survey, they looked at children’s shampoo and soap products available on online databases of six of the biggest retailers, and analyzed the top 20 best-selling products for each retailer in 2018. Of the unique products, CAPB was found to be an ingredient in 52% (39 of 75) of the shampoos and 44% (29 of 66) of the soap products. But each of these products “contained the term ‘hypoallergenic; on the product itself or in the product’s description,” they noted.

“CAPB is a prevalent sensitizer in pediatric patients and should be avoided in patients with AD,” the investigators wrote. That said, it’s not included among the 35 prevalent allergens in the T.R.U.E. test, and they recommended that pediatricians and dermatologists “be aware of common products containing CAPB when counseling patients about their product choices,” considering that CAPB sensitivity is more likely in patients with AD.

The study had no funding source, and the authors had no disclosures.

cpalmer@mdedge.com

SOURCE: Cho SI et al. J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2019.12.036.

In a survey of products labeled as hypoallergenic for children, about half of shampoos and almost 44% of soaps contained cocamidopropyl betaine (CAPB), a suspected sensitizer for hypersensitivity reactions in people with atopic dermatitis (AD) and allergic contact dermatitis, according to a research letter in the Journal of the American Academy of Dermatology.

Pirotehnik/iStock/Getty Images

In the letter, the authors, Reid W. Collis, of Washington University in St. Louis, and David M. Sheinbein, MD, of the division of dermatology at the university, referred to a previous study showing an association between contact sensitivity with CAPB and people with a history of AD. This was supported by the results of their own recent study in pediatric patients, they wrote, which found that reactions to CAPB were “exclusively” in patients with AD.

In the survey, they looked at children’s shampoo and soap products available on online databases of six of the biggest retailers, and analyzed the top 20 best-selling products for each retailer in 2018. Of the unique products, CAPB was found to be an ingredient in 52% (39 of 75) of the shampoos and 44% (29 of 66) of the soap products. But each of these products “contained the term ‘hypoallergenic; on the product itself or in the product’s description,” they noted.

“CAPB is a prevalent sensitizer in pediatric patients and should be avoided in patients with AD,” the investigators wrote. That said, it’s not included among the 35 prevalent allergens in the T.R.U.E. test, and they recommended that pediatricians and dermatologists “be aware of common products containing CAPB when counseling patients about their product choices,” considering that CAPB sensitivity is more likely in patients with AD.

The study had no funding source, and the authors had no disclosures.

cpalmer@mdedge.com

SOURCE: Cho SI et al. J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2019.12.036.

In a survey of products labeled as hypoallergenic for children, about half of shampoos and almost 44% of soaps contained cocamidopropyl betaine (CAPB), a suspected sensitizer for hypersensitivity reactions in people with atopic dermatitis (AD) and allergic contact dermatitis, according to a research letter in the Journal of the American Academy of Dermatology.

Pirotehnik/iStock/Getty Images

In the letter, the authors, Reid W. Collis, of Washington University in St. Louis, and David M. Sheinbein, MD, of the division of dermatology at the university, referred to a previous study showing an association between contact sensitivity with CAPB and people with a history of AD. This was supported by the results of their own recent study in pediatric patients, they wrote, which found that reactions to CAPB were “exclusively” in patients with AD.

In the survey, they looked at children’s shampoo and soap products available on online databases of six of the biggest retailers, and analyzed the top 20 best-selling products for each retailer in 2018. Of the unique products, CAPB was found to be an ingredient in 52% (39 of 75) of the shampoos and 44% (29 of 66) of the soap products. But each of these products “contained the term ‘hypoallergenic; on the product itself or in the product’s description,” they noted.

“CAPB is a prevalent sensitizer in pediatric patients and should be avoided in patients with AD,” the investigators wrote. That said, it’s not included among the 35 prevalent allergens in the T.R.U.E. test, and they recommended that pediatricians and dermatologists “be aware of common products containing CAPB when counseling patients about their product choices,” considering that CAPB sensitivity is more likely in patients with AD.

The study had no funding source, and the authors had no disclosures.

cpalmer@mdedge.com

SOURCE: Cho SI et al. J Am Acad Dermatol. 2020 May. doi: 10.1016/j.jaad.2019.12.036.

Major advances in understanding the nuanced mechanisms underlying atopic dermatitis have led to a plethora of novel topical, oral, and injectable biologic agents now in advanced-stage development, Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.

All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
 

Oral JAK inhibitors

The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.

“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.

Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.

“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.

Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.

Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.

The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.

Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.

Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.

“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.

Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.

All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.

“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.


 

Novel injectable biologics

Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.

Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.

But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).

“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.

It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.

Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.

“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.

Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
 

Nonsteroidal topical agents

These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.

These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

bjancin@mdedge.com

Major advances in understanding the nuanced mechanisms underlying atopic dermatitis have led to a plethora of novel topical, oral, and injectable biologic agents now in advanced-stage development, Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.

All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
 

Oral JAK inhibitors

The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.

“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.

Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.

“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.

Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.

Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.

The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.

Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.

Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.

“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.

Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.

All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.

“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.


 

Novel injectable biologics

Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.

Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.

But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).

“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.

It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.

Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.

“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.

Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
 

Nonsteroidal topical agents

These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.

These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

bjancin@mdedge.com

Major advances in understanding the nuanced mechanisms underlying atopic dermatitis have led to a plethora of novel topical, oral, and injectable biologic agents now in advanced-stage development, Jonathan I. Silverberg, MD, PhD, said during a virtual meeting held by the George Washington University department of dermatology. The virtual meeting included presentations that had been slated for the annual meeting of the American Academy of Dermatology, which was canceled due to the COVID-19 pandemic.

“In the next 2-3 years, we may have nine new treatments approved for atopic dermatitis,” said Dr. Silverberg, director of clinical research and contact dermatitis at the University.

All nine medications he discussed are either in ongoing pivotal phase 3 randomized controlled trials or have completed their phase 3 developmental programs. “This is not theoretical; these are things you’re going to be using in your toolbox imminently,” he stressed.
 

Oral JAK inhibitors

The Janus kinase (JAK) pathway is the intracellular signaling mediator that interacts with extracellular inflammatory cytokines, including interleukin-4, -13, and -31, which are familiar to dermatologists because they’re targeted by potent biologic monoclonal antibody therapies. For example, IL-4 goes through JAK1 and 3, while IL-31 signals through JAK1 and 2.

“You really need to know the key JAK and STAT pathways involved in atopic dermatitis because it will help you determine the selectivity of the agents you’re going to be using,” the dermatologist advised.

Three oral, once-daily JAK inhibitors – abrocitinib, upadacitinib, and baricitinib – are in an advanced stage of development.

“Upadacitinib and abrocitinib may be the two most potent options coming to market soon for us to be thinking about,” Dr. Silverberg said.

Abrocitinib: Three positive phase 3 studies featuring this selective JAK1 inhibitor have been completed in adults with moderate to severe atopic dermatitis (AD). The most recent, JADE COMPARE, featured a head-to-head randomized comparison of abrocitinib and the injectable IL-4/IL-13 inhibitor dupilumab. The results of this 837-patient study haven’t yet been formally presented at a conference because of the COVID-19 pandemic. However, Pfizer recently announced that abrocitinib at 200 mg/day achieved significantly greater improvements than dupilumab (Dupixent) in the coprimary endpoints of skin clearance as reflected in an Investigator’s Global Assessment (IGA) score of 0 or 1 (that is, clear or almost clear) and disease extent based upon 75% reduction from baseline in Eczema Area and Severity Index (EASI 75) at 12 weeks. The same was true at 16 weeks.

Also, a significantly larger proportion of abrocitinib-treated patients achieved at least a 4-point reduction in itch severity as measured using the Peak Pruritus Numerical Rating Scale at week 2. The company plans to file for regulatory approval later this year.

The JADE COMPARE data are exciting because of a pressing unmet need for treatment options that are even more powerful than dupilumab, Dr. Silverberg said.

Upadacitinib: This is selective JAK1 inhibitor is not as far along in the developmental pipeline as abrocitinib, but the efficacy appears to be comparable. In a phase 2 study of 126 adults with moderate to severe AD, upadacitinib at the top dose of 30 mg/day achieved efficacy results Dr. Silverberg deemed “quite extraordinary,” with a rate of IGA score of 0 or 1 of 50% at 16 weeks and an EASI 75 response rate of 69%. Those findings numerically eclipsed results seen in an earlier phase 3 pivotal trial for dupilumab, in which the IGA 0/1 rate was 37% and EASI 75 was 48%, albeit with the caveat that cross-trial comparisons must be taken with a large grain of salt.

Baricitinib: Multiple phase 3 studies of this JAK 1/2 inhibitor have reported positive results. At the top dose of 4 mg/day, baricitinib appears to be less effective than dupilumab in its earlier pivotal trials.

“This may be a good oral option for our patients. It could be similar to the Otezla [apremilast] story in psoriasis: It’s perhaps not as effective as a lot of the biologics, but patients often prefer an oral option,” Dr. Silverberg said.

Of note, in one large, placebo-controlled, phase 3 study of baricitinib on top of background low- or medium-potency topical steroids, the IGA 0/1 rate at 16 weeks with placebo plus topical steroids was a modest 14.7%, which underscores that this long-time workhorse topical therapy is objectively less effective than most physicians think. In contrast, the IGA 0/1 rate with baricitinib at 4 mg/day plus topical steroids was a more respectable 30.6%.

All three oral JAK inhibitors have rapid onset of efficacy, a key advantage over the biologic agents.

“The issue you have to keep in mind is safety. The safety in the atopic dermatitis population was overall quite good for all three drugs. However, safety concerns have come up with JAK inhibitors in rheumatoid arthritis. I think that’s the part we watch the most in this. The efficacy has become clear. Now the question is where does the safety take us,” he said.


 

Novel injectable biologics

Nemolizumab: This humanized monoclonal antibody inhibits IL-31 receptor alpha. Mounting evidence implicates IL-31 as both a proinflammatory and immunomodulatory cytokine linking the immune and neural systems.

Early on, most researchers pigeonholed IL-31 as being a key player only in the itch factor in AD. Not so. Indeed, Dr. Silverberg was the lead investigator in a recent phase 2b study of nemolizumab that demonstrated the biologic is also effective at rapidly clearing AD lesions. The study, which evaluated three different doses in 226 adults with moderate to severe AD and severe pruritus who were on background topical corticosteroids, showed that nemolizumab at 30 mg every 4 weeks trounced placebo in terms of itch reduction: The 69% drop from baseline in Peak Pruritus Numeric Rating Scale at week 16 was twice that in controls, with a significant difference apparent even at week 1.

But in addition, the 33% IGA 0/1 rate at the same time point bested the 12% rate in controls. The EASI 75 response rate was significantly higher as well – 49% versus 19% – as was the EASI 90 response of 33%, compared with 9% in controls. Moreover, nemolizumab-treated patients used close to 40% less topical steroids during the study (J Allergy Clin Immunol. 2020 Jan;145[1]:173-82).

“This is something that’s fascinating. The study gets into the idea that a subset of atopic dermatitis patients have the itch that rashes, and perhaps if you break the itch/scratch cycle you can modify the lesions. Or the effect may even be due to the direct anti-inflammatory action of IL-31 blockade,” Dr. Silverberg observed.

It appeared that a plateau hadn’t been reached for some endpoints out at week 24, when the study ended. Japanese phase 3 studies have been completed, with what he called “great results,” and others are ongoing in the United States.

Tralokinumab: This fully human monoclonal antibody binds to IL-13, but unlike dupilumab, it doesn’t also inhibit IL-4. Tralokinumab met all primary and secondary endpoints in three pivotal phase 3 clinical trials, known as ECZTRA 1-3, that assessed it as treatment for moderate to severe AD in adults and showed an overall adverse event rate comparable with placebo. Leo Pharma, the Danish company developing the biologic, has announced it will file for marketing approval before the end of 2020. Phase 3 data would have been presented at the annual meeting of the American Academy of Dermatology in Denver, had it not been canceled. Dr. Silverberg said that, based upon phase 2 results, it appears tralokinumab may not be quite as effective as dupilumab in the overall AD population, but he predicted the newcomer will still play a useful role.

“The complexities of the immune system are such that some patients will respond better to one drug than another. I think we still have a lot to learn about who the patients are for these novel assets,” he said.

Lebrikizumab: This is another selective IL-13 inhibitor, but this one binds to IL-13 in a slightly different way than tralokinumab. The Food and Drug Administration granted it Fast Track status in December 2019. Twin placebo-controlled phase 3 studies of lebrikizumab as monotherapy for moderate to severe AD are ongoing, and another phase 3 trial of the biologic in combination with topical steroids is planned. Based upon the results of a phase 2b study, the highest dose studied – 250 mg every 2 weeks – appears to be at least as effective as dupilumab.
 

Nonsteroidal topical agents

These three late-stage topical creams – ruxolitinib, delgocitinib, and tapinarof – have previously received considerable coverage in Dermatology News. Ruxolitinib, a selective JAK1/2 inhibitor, has completed a positive phase 3 trial in adolescents and adults with mild to moderate AD. Delgocitinib, a pan-JAK1/2/3 and Tyrosine kinase 2 inhibitor, is already approved in an ointment formulation in Japan, and the cream formulation is in phase 2 studies in the United States and Europe. Tapinarof has a unique mechanism of action – it’s an aryl hydrocarbon receptor modulator – and is now in phase 3 in adolescents and adults with moderate to severe AD.

These three drugs appear to offer efficacy that’s comparable to or even better than medium-potency topical steroids, and without the notorious steroidal side effects that have caused widespread parental steroid-phobia. Potential applications for other inflammatory diseases, including vitiligo and psoriasis, are under study.

Dr. Silverberg reported receiving research grants from Galderma and GlaxoSmithKline and serving as a consultant to those pharmaceutical companies and more than a dozen others.

bjancin@mdedge.com

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

aotto@mdedge.com

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

aotto@mdedge.com

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

Use of biologics and Janus kinase (JAK) inhibitors was not associated with worse outcomes in 86 people with inflammatory diseases who contracted COVID-19, according to a case series from New York University Langone Health.

“We are not seeing worse outcomes with overall use of either. It’s reassuring” that the data support continued use during the pandemic, said rheumatologist and senior investigator Jose Scher, MD, an associate professor at New York University.

There have been concerns among rheumatologists, gastroenterologists, and dermatologists that underlying inflammatory diseases and the agents used to treat them would impact outcomes in COVID-19.

Dr. Scher and colleagues, including lead author and rheumatologist Rebecca Haberman, MD, wanted to address the issue, so they reviewed the experience in their own health system of patients with inflammatory diseases – most commonly psoriatic arthritis, RA, and Crohn’s disease – who were assessed for COVID-19 from March 3 to April 3.

Fever, cough, and shortness of breath were the most common symptoms. The infection was confirmed by polymerase chain reaction in 59 (69%) and highly suspected in 27.

A total of 62 patients (72%) were on JAK inhibitors or biologics at baseline, including 38 (44%) on tumor necrosis factor inhibitors.

Overall, 14 patients (16%) were hospitalized with COVID-19, which is consistent the 26% hospitalization rate among the general population in New York City.

Baseline biologic and JAK inhibitor use was actually lower among hospitalized patients than among those who weren’t hospitalized (50% vs. 76%), and the hospitalization rate was only 11% among 62 subjects who had been on the agents long term, more than a year among most.

Hospitalized patients tended to be slightly older (mean, 50 vs. 46 years) with a higher prevalence of hypertension, diabetes, and chronic obstructive pulmonary disease. They also had a higher prevalence of RA (43% vs. 19%), methotrexate use (43% vs. 15%), and use of hydroxychloroquine (21% vs. 7%) and oral glucocorticoids (29% vs. 6%).

It’s unknown what to make of those findings for now, Dr. Scher said. The study didn’t address differences in the severity of the underlying inflammatory illness, but a new and significantly larger case series is in the works that will analyze that and other potential confounders.

Dr. Scher noted that he’s particularly interested in drilling down further on the higher prevalence of RA and methotrexate in hospitalized patients. “We want to understand those signals better. All of this needs further validation,” he said.

Of the 14 hospitalized patients, 11 (79%) were discharged after a mean of 5.6 days. One died in the ED, and two remained hospitalized as of April 3, including one in the ICU.

The investigators are contributing to COVID-19 registries for inflammatory disease patients. The registries are tending to report higher hospitalization rates, but Dr. Scher noted they might be biased towards more severe cases, among other issues.

As for the current situation in New York City, he said that the “last week in March and first 3 in April were indescribable in terms of admissions, intubations, and deaths. Over the last week or so, it has calmed down significantly.”

There was no external funding. Dr. Haberman reported ties to Janssen, and Dr. Scher reported ties to Janssen, Novartis, Pfizer, and other companies.

aotto@mdedge.com

SOURCE: Haberman R et al. N Engl J Med. 2020 Apr 29. doi: 10.1056/NEJMc2009567.

The papules were clinically consistent with Kaposi sarcoma (KS) and confirmed with a biopsy from the buccal mucosa. The patient had not been given a diagnosis of human immunodeficiency virus (HIV) prior to this presentation. However, the physician confirmed the diagnosis with RNA titers. A CD4 count < 40 cells/mm³ (reference range, 500-1200 cells/mm³) pointed to her progression to AIDS. A chest X-ray revealed multiple nodules; a subsequent biopsy indicated that they were consistent with KS.

KS is a low-grade tumor of vascular origin associated with human herpesvirus-8 (HHV-8). It most often presents on the skin as flat to raised pink to deep purple lesions. It can manifest in the oral mucosa, viscera, and other organs, which can portend a worse prognosis because of the risks associated with bleeding and organ perforation.

There are 4 types of KS.

• Classic KS occurs most often in elderly men of Mediterranean descent.
• HIV-associated KS can occur at any time during HIV infection but is more common as CD4 counts fall. HIV-associated KS increased in frequency dramatically in the United States during the early years of the HIV pandemic prior to effective antiretroviral therapy (ART).
• Endemic KS occurs in equatorial Africa, where there is a natural increased transmission rate of HHV-8.
• Iatrogenic KS can occur following treatment with immunosuppressive therapies.

Our patient was admitted to the Infectious Disease Service and given ART. Chemotherapy was discussed (and sometimes is warranted in extensive visceral disease) but the patient and her specialists opted for ART alone. In addition to ART, she was started on daily trimethoprim-sulfamethoxazole for pneumocystis prophylaxis.

At 6 months’ follow-up with Infectious Disease, the patient’s oral lesions resolved, CD4 count increased above 200 cells/mm³, and HIV RNA titers fell.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The papules were clinically consistent with Kaposi sarcoma (KS) and confirmed with a biopsy from the buccal mucosa. The patient had not been given a diagnosis of human immunodeficiency virus (HIV) prior to this presentation. However, the physician confirmed the diagnosis with RNA titers. A CD4 count < 40 cells/mm³ (reference range, 500-1200 cells/mm³) pointed to her progression to AIDS. A chest X-ray revealed multiple nodules; a subsequent biopsy indicated that they were consistent with KS.

KS is a low-grade tumor of vascular origin associated with human herpesvirus-8 (HHV-8). It most often presents on the skin as flat to raised pink to deep purple lesions. It can manifest in the oral mucosa, viscera, and other organs, which can portend a worse prognosis because of the risks associated with bleeding and organ perforation.

There are 4 types of KS.

• Classic KS occurs most often in elderly men of Mediterranean descent.
• HIV-associated KS can occur at any time during HIV infection but is more common as CD4 counts fall. HIV-associated KS increased in frequency dramatically in the United States during the early years of the HIV pandemic prior to effective antiretroviral therapy (ART).
• Endemic KS occurs in equatorial Africa, where there is a natural increased transmission rate of HHV-8.
• Iatrogenic KS can occur following treatment with immunosuppressive therapies.

Our patient was admitted to the Infectious Disease Service and given ART. Chemotherapy was discussed (and sometimes is warranted in extensive visceral disease) but the patient and her specialists opted for ART alone. In addition to ART, she was started on daily trimethoprim-sulfamethoxazole for pneumocystis prophylaxis.

At 6 months’ follow-up with Infectious Disease, the patient’s oral lesions resolved, CD4 count increased above 200 cells/mm³, and HIV RNA titers fell.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

The papules were clinically consistent with Kaposi sarcoma (KS) and confirmed with a biopsy from the buccal mucosa. The patient had not been given a diagnosis of human immunodeficiency virus (HIV) prior to this presentation. However, the physician confirmed the diagnosis with RNA titers. A CD4 count < 40 cells/mm³ (reference range, 500-1200 cells/mm³) pointed to her progression to AIDS. A chest X-ray revealed multiple nodules; a subsequent biopsy indicated that they were consistent with KS.

KS is a low-grade tumor of vascular origin associated with human herpesvirus-8 (HHV-8). It most often presents on the skin as flat to raised pink to deep purple lesions. It can manifest in the oral mucosa, viscera, and other organs, which can portend a worse prognosis because of the risks associated with bleeding and organ perforation.

There are 4 types of KS.

• Classic KS occurs most often in elderly men of Mediterranean descent.
• HIV-associated KS can occur at any time during HIV infection but is more common as CD4 counts fall. HIV-associated KS increased in frequency dramatically in the United States during the early years of the HIV pandemic prior to effective antiretroviral therapy (ART).
• Endemic KS occurs in equatorial Africa, where there is a natural increased transmission rate of HHV-8.
• Iatrogenic KS can occur following treatment with immunosuppressive therapies.

Our patient was admitted to the Infectious Disease Service and given ART. Chemotherapy was discussed (and sometimes is warranted in extensive visceral disease) but the patient and her specialists opted for ART alone. In addition to ART, she was started on daily trimethoprim-sulfamethoxazole for pneumocystis prophylaxis.

At 6 months’ follow-up with Infectious Disease, the patient’s oral lesions resolved, CD4 count increased above 200 cells/mm³, and HIV RNA titers fell.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

Many questions on the care of patients with regard to COVID-19 have been coming up in clinic lately. We periodically try to answer some of the most common and important ones, including the following:

Courtesy NIAID-RML

Question

How should patients on immunosuppressive therapy be advised during the COVID-19 pandemic?

Answer

In general, those patients who have not tested positive, have not been exposed, and are asymptomatic should continue their medications as prescribed.

The American College of Rheumatology issued a statement on April 14, recommending that stable patients continue their medications. Those with known exposure but without confirmed infection may continue hydroxychloroquine, sulfasalazine, and NSAIDs.

Immunosuppressants, non–IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily, pending a negative test or after two weeks without symptoms. In patients with confirmed positive COVID-19 infection, sulfasalazine, methotrexate, leflunomide, immunosuppressants, non-IL-6 biologics, and JAK inhibitors should be stopped temporarily. Anti-malarial therapies (hydroxycholoroquine and chloroquine) may be continued and IL-6 inhibitors may be continued in select circumstances.¹

The American Academy of Dermatology recommends that the discussion of continuation of biologics be based on a case-by-case basis, citing insufficient evidence to recommend against discontinuation at this time in those patients who have not tested positive. In patients who have tested positive for COVID-19 it is recommended that biologic therapy be suspended until symptoms have resolved.²

Question

Should I continue preventive services during peak COVID-19?

Answer

The Centers for Disease Control and Prevention recommends delaying all elective ambulatory provider visits. In general, preventative services, such as adult immunizations, lipid screening, and cancer screenings, should be delayed. Additionally, the CDC recommends reaching out to patients who are at high risk for complications from respiratory diseases to ensure medication adherence and provide resources if these patients become ill. Facilities can reduce transmission of COVID-19 by triaging and assessing patients through virtual visits through phone calls, video conferences, text-monitoring systems, and other telemedicine tools. Physicians should try to provide routine and chronic care through virtual visits when possible over in-person visits.³

Question

Should I continue to vaccinate my pediatric population during peak COVID-19?

Answer

Practices that schedule separate well visits and sick visits in different sessions or locations can continue to provide well child visits. A practice could, for example, schedule well visits in the morning and sick visits in the afternoon if a single facility is used. These practices should prioritize newborn care and vaccinations of children, especially for those under the age of 24 months.⁴

Question

Can physicians use telehealth (phone only or audiovisual) to conduct visits with Medicare patients even if they are new patients?

Answer

Effective March 1 through the duration of the pandemic, Medicare will pay physicians for telehealth services at the same rate as an in-office visit. On March 30th, the Centers for Medicare & Medcaid Services announced new policies for physicians and hospitals during the COVID-19 pandemic. These guidelines were updated on April 9.

Audio-only visits are now permitted and the limit on the number of these kinds of visits allowed per month has been waived. Controlled substances can be prescribed via telehealth; however, complying with each state’s individual laws is still required.

Use of any two-way, audiovisual device is permitted. The level of service billed for visits with both audio and visual components is the same as an in-office visit. Telemedicine can be used for both new and existing patients.⁵

A list of services that may be rendered via telehealth are available on the CMS website.⁶


It will be important to regularly check the references given, as information on some of these topics is updated frequently.
 

Dr. Chuong is a second-year resident in the family medicine residency, Dr. Flanagan is a third-year resident, and Dr. Matthews is an intern, all at Abington (Pa.) Jefferson Health. Dr. Skolnik is professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Jefferson Health.

References

1. ACR issues COVID-19 treatment guidance for rheumatic disease patients.

2. American Academy of Dermatology: Guidance on the use of biologic agents during COVID-19 outbreak.

3. Centers for Disease Control and Prevention. Actions to take in response to community transmission of COVID-19.

4. Centers for Disease Control and Prevention. Maintaining childhood immunizations during COVID19 pandemic.

5. Centers for Medicare & Medcaid Services. COVID-19 frequently asked questions (FAQs) on Medicare Fee-for-Service (FFS) billing.

6. Centers for Medicare & Medcaid Services. List of telehealth services.
 

This patient had prurigo nodularis (PN). The diagnosis usually is made clinically by the appearance of the lesions and the cycle of severe pruritus and scratching. In this case, the patient had acutely excoriated lesions in addition to more chronic lesions that had become hyperpigmented nodules. The distribution pattern on his back was typical and highlighted the clinical course of PN. There were no lesions present where the patient was unable to scratch; however, lesions were present where he could reach, hence the term Picker’s nodules. Often, these patients have a history of atopic dermatitis, and anxiety may play a role in patients nervously scratching the lesions.

Biopsy is indicated if there is suspicion of bullous pemphigoid or cutaneous T-cell lymphoma. Pathology of PN shows increased density of nerve fibers in the dermis along with an increased number of T cells, mast cells, and eosinophilic granulocytes. Most patients do not require biopsy unless the diagnosis is in doubt.

Treatment can be difficult due to the severe pruritis and subsequent scratching that appears to prolong the chronic cycle of inflammation. Daily use of nonsedating antihistamines (eg, loratadine, cetirizine) may help reduce pruritus and break the cycle. Sedating antihistamines (eg, diphenhydramine, hydroxyzine) can be used cautiously at bedtime; cotton gloves worn while sleeping may reduce nocturnal scratching and excoriations.

Topical steroids (eg, triamcinolone, betamethasone) can reduce the itching and local inflammation. Emollients can help with associated dyshidrosis and eczema, if present.

Second line therapies include topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus), calcipotriene, and narrow beam UVB therapy.

This patient had done reasonably well with cetirizine and triamcinolone in the past, so treatment was restarted. He was counseled regarding the nature and chronicity of his PN and told that if he could achieve symptom control and stop scratching the lesions, his condition might resolve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had prurigo nodularis (PN). The diagnosis usually is made clinically by the appearance of the lesions and the cycle of severe pruritus and scratching. In this case, the patient had acutely excoriated lesions in addition to more chronic lesions that had become hyperpigmented nodules. The distribution pattern on his back was typical and highlighted the clinical course of PN. There were no lesions present where the patient was unable to scratch; however, lesions were present where he could reach, hence the term Picker’s nodules. Often, these patients have a history of atopic dermatitis, and anxiety may play a role in patients nervously scratching the lesions.

Biopsy is indicated if there is suspicion of bullous pemphigoid or cutaneous T-cell lymphoma. Pathology of PN shows increased density of nerve fibers in the dermis along with an increased number of T cells, mast cells, and eosinophilic granulocytes. Most patients do not require biopsy unless the diagnosis is in doubt.

Treatment can be difficult due to the severe pruritis and subsequent scratching that appears to prolong the chronic cycle of inflammation. Daily use of nonsedating antihistamines (eg, loratadine, cetirizine) may help reduce pruritus and break the cycle. Sedating antihistamines (eg, diphenhydramine, hydroxyzine) can be used cautiously at bedtime; cotton gloves worn while sleeping may reduce nocturnal scratching and excoriations.

Topical steroids (eg, triamcinolone, betamethasone) can reduce the itching and local inflammation. Emollients can help with associated dyshidrosis and eczema, if present.

Second line therapies include topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus), calcipotriene, and narrow beam UVB therapy.

This patient had done reasonably well with cetirizine and triamcinolone in the past, so treatment was restarted. He was counseled regarding the nature and chronicity of his PN and told that if he could achieve symptom control and stop scratching the lesions, his condition might resolve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had prurigo nodularis (PN). The diagnosis usually is made clinically by the appearance of the lesions and the cycle of severe pruritus and scratching. In this case, the patient had acutely excoriated lesions in addition to more chronic lesions that had become hyperpigmented nodules. The distribution pattern on his back was typical and highlighted the clinical course of PN. There were no lesions present where the patient was unable to scratch; however, lesions were present where he could reach, hence the term Picker’s nodules. Often, these patients have a history of atopic dermatitis, and anxiety may play a role in patients nervously scratching the lesions.

Biopsy is indicated if there is suspicion of bullous pemphigoid or cutaneous T-cell lymphoma. Pathology of PN shows increased density of nerve fibers in the dermis along with an increased number of T cells, mast cells, and eosinophilic granulocytes. Most patients do not require biopsy unless the diagnosis is in doubt.

Treatment can be difficult due to the severe pruritis and subsequent scratching that appears to prolong the chronic cycle of inflammation. Daily use of nonsedating antihistamines (eg, loratadine, cetirizine) may help reduce pruritus and break the cycle. Sedating antihistamines (eg, diphenhydramine, hydroxyzine) can be used cautiously at bedtime; cotton gloves worn while sleeping may reduce nocturnal scratching and excoriations.

Topical steroids (eg, triamcinolone, betamethasone) can reduce the itching and local inflammation. Emollients can help with associated dyshidrosis and eczema, if present.

Second line therapies include topical calcineurin inhibitors (eg, tacrolimus, pimecrolimus), calcipotriene, and narrow beam UVB therapy.

This patient had done reasonably well with cetirizine and triamcinolone in the past, so treatment was restarted. He was counseled regarding the nature and chronicity of his PN and told that if he could achieve symptom control and stop scratching the lesions, his condition might resolve.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its safety review of ingenol mebutate (Picato), finding that the risks for skin cancer from the topical gel used to treat actinic keratosis outweigh the benefits.

Picato was cleared for marketing in the European Union in November 2012. The European Commission requested a safety review of the drug in September 2019 after data suggested a higher number of skin cancer cases, including cases of squamous cell carcinoma, in patients using it, as reported by Medscape Medical News.

In January 2020, use of Picato was suspended as a precaution while the PRAC review was underway. One month later, marketing authorization was withdrawn at the request of Leo Laboratories Ltd, which marketed the medicine.

The PRAC has now concluded its review of all available data on the risk for skin cancer in patients using Picato, including results of a study that compared Picato with imiquimod.

The review found “a higher occurrence of skin cancers, especially squamous cell carcinoma, in areas of skin treated with Picato than in areas treated with imiquimod,” the EMA said Friday in a news release.

“The committee also considered that Picato’s effectiveness is not maintained over time and noted that other treatment options are available for actinic keratosis,” the EMA said.

The agency recommends that patients who have used Picato watch for unusual skin changes or growths, which may occur weeks to months after use, and seek medical advice if any occur.

Picato continues to be available in the United States, although the US Food and Drug Administration is also looking into its safety and risks.

This article first appeared on Medscape.com.

The European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its safety review of ingenol mebutate (Picato), finding that the risks for skin cancer from the topical gel used to treat actinic keratosis outweigh the benefits.

Picato was cleared for marketing in the European Union in November 2012. The European Commission requested a safety review of the drug in September 2019 after data suggested a higher number of skin cancer cases, including cases of squamous cell carcinoma, in patients using it, as reported by Medscape Medical News.

In January 2020, use of Picato was suspended as a precaution while the PRAC review was underway. One month later, marketing authorization was withdrawn at the request of Leo Laboratories Ltd, which marketed the medicine.

The PRAC has now concluded its review of all available data on the risk for skin cancer in patients using Picato, including results of a study that compared Picato with imiquimod.

The review found “a higher occurrence of skin cancers, especially squamous cell carcinoma, in areas of skin treated with Picato than in areas treated with imiquimod,” the EMA said Friday in a news release.

“The committee also considered that Picato’s effectiveness is not maintained over time and noted that other treatment options are available for actinic keratosis,” the EMA said.

The agency recommends that patients who have used Picato watch for unusual skin changes or growths, which may occur weeks to months after use, and seek medical advice if any occur.

Picato continues to be available in the United States, although the US Food and Drug Administration is also looking into its safety and risks.

This article first appeared on Medscape.com.

The European Medicines Agency’s (EMA’s) Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its safety review of ingenol mebutate (Picato), finding that the risks for skin cancer from the topical gel used to treat actinic keratosis outweigh the benefits.

Picato was cleared for marketing in the European Union in November 2012. The European Commission requested a safety review of the drug in September 2019 after data suggested a higher number of skin cancer cases, including cases of squamous cell carcinoma, in patients using it, as reported by Medscape Medical News.

In January 2020, use of Picato was suspended as a precaution while the PRAC review was underway. One month later, marketing authorization was withdrawn at the request of Leo Laboratories Ltd, which marketed the medicine.

The PRAC has now concluded its review of all available data on the risk for skin cancer in patients using Picato, including results of a study that compared Picato with imiquimod.

The review found “a higher occurrence of skin cancers, especially squamous cell carcinoma, in areas of skin treated with Picato than in areas treated with imiquimod,” the EMA said Friday in a news release.

“The committee also considered that Picato’s effectiveness is not maintained over time and noted that other treatment options are available for actinic keratosis,” the EMA said.

The agency recommends that patients who have used Picato watch for unusual skin changes or growths, which may occur weeks to months after use, and seek medical advice if any occur.

Picato continues to be available in the United States, although the US Food and Drug Administration is also looking into its safety and risks.

This article first appeared on Medscape.com.