Contact Dermatitis

The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy

In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).

Figure 1. Left arm with tender stellate purpura (A). Left side of the lower back with large area of purpura and few scattered tense bullae (B).

Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.¹ Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.

Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.² Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.³

Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)⁴; oral mucosal involvement also has been reported.⁵ Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.^3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.⁴ Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.⁶ On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.

Figure 2. Biopsy of the left arm revealed subepidermal detachment with a neutrophilic infiltrate (A)(H&E, original magnification ×40) and perivascular neutrophilic infiltration with nuclear debris and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (B)(H&E, original magnification ×100).

Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.⁷ Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.⁸

Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).⁹ Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.⁹

Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.¹ Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.¹⁰ Oral prednisone and colchicine also have been used with reported success.⁵

Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.

The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy

In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).

Figure 1. Left arm with tender stellate purpura (A). Left side of the lower back with large area of purpura and few scattered tense bullae (B).

Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.¹ Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.

Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.² Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.³

Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)⁴; oral mucosal involvement also has been reported.⁵ Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.^3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.⁴ Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.⁶ On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.

Figure 2. Biopsy of the left arm revealed subepidermal detachment with a neutrophilic infiltrate (A)(H&E, original magnification ×40) and perivascular neutrophilic infiltration with nuclear debris and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (B)(H&E, original magnification ×100).

Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.⁷ Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.⁸

Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).⁹ Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.⁹

Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.¹ Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.¹⁰ Oral prednisone and colchicine also have been used with reported success.⁵

Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.

The Diagnosis: Levamisole-Induced Cutaneous Vasculopathy

In our patient, tender stellate purpura and occasional bullae were present on the ears, arms and legs, groin, and buttocks (Figure 1). Histopathologic examination revealed subepidermal detachment, perivascular neutrophilic infiltrate, and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (Figure 2).

Figure 1. Left arm with tender stellate purpura (A). Left side of the lower back with large area of purpura and few scattered tense bullae (B).

Levamisole-induced vasculopathy is a condition related primarily to cocaine use. Levamisole is an immunomodulatory agent, historically used as a disease-modifying antirheumatic drug for rheumatoid arthritis and as adjuvant chemotherapy for various types of cancer. However, levamisole for human use was banned from US and Canadian markets in 1999 and 2003, respectively, due to increased risk for agranulocytosis, retiform purpura, and epilepsy.¹ Currently, veterinarians use levamisole as an anthelminthic agent to deworm house and farm animals. In Europe, pediatric nephrologists use it as a steroid-sparing agent in children with steroid-dependent nephritic syndrome.

Over the last decade, levamisole has increasingly been used as a cocaine adulterant or bulking agent. This contaminant closely resembles cocaine physically and is theorized to prolong or attenuate cocaine’s “high.” Approximately 69% of cocaine sampled by the US Drug Enforcement Administration is adulterated with levamisole.² Similarly, levamisole-contaminated cocaine also has been found in Europe, Australia, and other parts of the world. Potential complications include vasculitis, thromboembolism, neutropenia, and agranulocytosis.³

Levamisole-induced vasculopathy appears to affect cocaine users of all ages, ethnicities, and genders. Cocaine can be smoked, snorted, or injected. In nearly all reported cases, patients characteristically present with hemorrhagic bullae of the bilateral ear helix, cheeks, or nasal tip. Any body site can be affected with retiform purpura or necrotic bullae. Along with skin lesions, arthralgia is commonly reported, as are constitutional symptoms (eg, fever, night sweats, weight loss, malaise)⁴; oral mucosal involvement also has been reported.⁵ Laboratory investigation can reveal neutropenia, positive antineutrophil cytoplasmic antibodies (ANCAs) in the perinuclear or cytoplasmic pattern, positive proteinase 3, and negative or mildly elevated antimyeloperoxidase.^3-5 Acute renal injury and pulmonary hemorrhage are other potentially serious copmlications.⁴ Antihuman neutrophil elastase antibody testing can help distinguish levamisole-induced vasculopathy from other forms of immune-mediated vasculitis and will be negative in immune-mediated vasculitides such as Churg-Strauss syndrome (allergic granulomatosis), Wegener granulomatosis (granulomatosis with polyangiitis), and polyarteritis nodosa.⁶ On histology, microvascular thrombosis or leukocytoclastic vasculitis can both, or individually, be seen. Epidermal necrosis, dermal hemorrhage, and endothelial hyperplasia have all been noted in skin biopsied from necrotic bullae.

Figure 2. Biopsy of the left arm revealed subepidermal detachment with a neutrophilic infiltrate (A)(H&E, original magnification ×40) and perivascular neutrophilic infiltration with nuclear debris and red blood cell extravasation, consistent with early leukocyctoclastic vasculitis (B)(H&E, original magnification ×100).

Levamisole’s short half-life (approximately 5–6 hours) makes it difficult to detect on routine blood draws. An astute physician suspecting this diagnosis on initial presentation can ask for levamisole detection on urine toxicology screening.⁷ Urine samples also can be sent for testing with gas chromatography–mass spectrometry, though this test may only be available at major research centers.⁸

Differential diagnosis of levamisole toxicity includes different types of vasculitides such as cryoglobulinemia (positive serum IgM and IgG cryoglobulins; possible hepatitis C infection), Wegener granulomatosis (cytoplasmic ANCA positive; associated with upper and lower respiratory tract inflammation, glomerulonephritis), Churg-Strauss syndrome (perinuclear ANCA positive; associated with asthma and eosinophilia), and polyarteritis nodosa (medium vessel involvement only; associated with livedo reticularis, subcutaneous nodules, ulcers).⁹ Necrotic lesions also may raise the possibility of warfarin necrosis, heparin necrosis, or cholesterol emboli. Cholesterol embolism most frequently presents with small vessel vasculitis and necrosis of distal extremities such as the toes. With large areas of skin involvement and bullae, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis also should be considered.⁹

Definitive treatment of this condition requires complete and immediate cessation of cocaine use. Levamisole also has been found as a contaminant in heroin.¹ Thus, it may be prudent to recommend heroin avoidance to the patient to prevent recurrences. Management of acute levamisole-induced vasculopathy is primarily symptomatic. Some patients with severe neutropenia at risk for infection have been treated with granulocyte colony-stimulating factor, while others have only required pain control, usually with nonsteroidal anti-inflammatory drugs.¹⁰ Oral prednisone and colchicine also have been used with reported success.⁵

Given the increasing incidence of levamisole toxicity and public health implications, clinicians should be aware of this association and the classic clinical and laboratory findings.

1. Which of the following is not a component of fragrance mix?

a. abietic acid

b. α-amylcinnamaldehyde

c. geraniol

d. hydroxycitronellal

e. oakmoss

2. A patient is referred for patch testing for suspected allergic contact dermatitis and is found to have positivity to disperse blue dye 106. The patient should avoid all of the following except:

a. black-colored clothing

b. pure acetate clothing

c. pure polyester clothing

d. purple-colored clothing

e. red-colored clothing

3. A patient with a documented contact allergy to ethylenediamine dihydrochloride should avoid all of the following systemic medications except:

a. aminophylline

b. disulfiram

c. hydroxyzine

d. meclizine

e. promethazine

4. Formaldehyde can cross-react with all of the following except:

a. diazolidinyl urea

b. DMDM hydantoin

c. imidazolidinyl urea

d. para-aminobenzoic acid

e. quaternium-15

5. Colophony can be found in all of the following trees except:

a. cedars

b. firs

c. junipers

d. maples

e. pines

1. Which of the following is not a component of fragrance mix?

a. abietic acid

b. α-amylcinnamaldehyde

c. geraniol

d. hydroxycitronellal

e. oakmoss

2. A patient is referred for patch testing for suspected allergic contact dermatitis and is found to have positivity to disperse blue dye 106. The patient should avoid all of the following except:

a. black-colored clothing

b. pure acetate clothing

c. pure polyester clothing

d. purple-colored clothing

e. red-colored clothing

3. A patient with a documented contact allergy to ethylenediamine dihydrochloride should avoid all of the following systemic medications except:

a. aminophylline

b. disulfiram

c. hydroxyzine

d. meclizine

e. promethazine

4. Formaldehyde can cross-react with all of the following except:

a. diazolidinyl urea

b. DMDM hydantoin

c. imidazolidinyl urea

d. para-aminobenzoic acid

e. quaternium-15

5. Colophony can be found in all of the following trees except:

a. cedars

b. firs

c. junipers

d. maples

e. pines

1. Which of the following is not a component of fragrance mix?

a. abietic acid

b. α-amylcinnamaldehyde

c. geraniol

d. hydroxycitronellal

e. oakmoss

2. A patient is referred for patch testing for suspected allergic contact dermatitis and is found to have positivity to disperse blue dye 106. The patient should avoid all of the following except:

a. black-colored clothing

b. pure acetate clothing

c. pure polyester clothing

d. purple-colored clothing

e. red-colored clothing

3. A patient with a documented contact allergy to ethylenediamine dihydrochloride should avoid all of the following systemic medications except:

a. aminophylline

b. disulfiram

c. hydroxyzine

d. meclizine

e. promethazine

4. Formaldehyde can cross-react with all of the following except:

a. diazolidinyl urea

b. DMDM hydantoin

c. imidazolidinyl urea

d. para-aminobenzoic acid

e. quaternium-15

5. Colophony can be found in all of the following trees except:

a. cedars

b. firs

c. junipers

d. maples

e. pines

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

The use of lasers in dermatology has had a major impact on the treatment of many dermatologic conditions. In this column practical applications of lasers in medical dermatology will be discussed to give dermatology residents a broad overview of both established indications and the reasoning behind the usage of lasers in treating these skin conditions. The applications for lasers in aesthetic dermatology are numerous and are constantly being refined and developed; they have been discussed extensively in the literature. Given the vast variety of uses of lasers in dermatology today, a comprehensive review of this topic would likely span several volumes. This article will focus on recent evidence regarding the use of lasers in medical dermatology, specifically laser treatment of selected common dermatoses and cutaneous malignancies.

Laser Treatment of Skin Diseases

Many common dermatoses seen in the dermatologist’s office (eg, discoid lupus erythematosus [DLE], morphea, alopecia) already have an established therapeutic ladder, with most patients responding to either first- or second-line therapies; however, a number of patients present with refractory disease that can be difficult to treat due to either treatment resistance or other contraindications to therapy. With the advent and development of modern lasers, we are now able to target many of these conditions and provide a viable safe treatment option for these patients. Although many physicians may be familiar with the use of the excimer laser in the treatment of psoriasis,¹ a long-standing and well-accepted treatment modality for this condition, many novel applications for different types of lasers have been developed.

First, it is important to consider what a laser is able to accomplish to modulate the skin. With ablative lasers such as the CO₂ laser, it is possible to destroy superficial layers of the skin (ie, the epidermis). It would stand to reason that this approach would be ideal for treating epidermal processes such as viral warts; in fact, this modality has been used for this indication for more than 3 decades, with the earliest references coming from the podiatric and urologic literature.^2,3 Despite conflicting reports of the risk for human papillomavirus aerosolization and subsequent contamination of the treatment area,^4,5 CO₂ laser therapy has been advocated as a nonsurgical approach to difficult-to-treat cases of viral warts.

On the other hand, the pulsed dye laser (PDL) can target blood vessels because the wavelength corresponds to the absorption spectrum of hemoglobin and penetrates to the level of the dermis, while the pulse duration can be set to be shorter than the thermal relaxation time of a small cutaneous blood vessel.⁶ In clinical practice, the PDL has been used for the treatment of vascular lesions including hemangiomas, nevus flammeus, and other vascular proliferations.^7-9 However, the PDL also can be used to target the vessels in cutaneous inflammatory diseases that feature vascular dilation and/or perivascular inflammation as a prominent feature.

Discoid lupus erythematosus is a form of chronic cutaneous lupus erythematosus that may be difficult to treat, with recalcitrant lesions displaying continued inflammation leading to chronic scarring and dyspigmentation. A small study (N=12) presented the efficacy of the PDL in the treatment of DLE lesions, suggesting that it has good efficacy in treating recalcitrant lesions with significant reduction in the cutaneous lupus erythematosus disease area and severity index after 6 weeks of treatment and 6 weeks of follow-up (P<.0001) with decreased erythema and scaling.¹⁰ It is important to note, however, that scarring, dyspigmentation, and atrophy were not affected, which suggests that early intervention may be optimal to prevent development of these sequelae. More interestingly, a more recent study expounded on this idea and attempted to examine pathophysiologic mechanisms behind this observed improvement. Evaluation of biopsy specimens before and after treatment and immunohistochemistry revealed that PDL treatment of cutaneous DLE lesions led to a decrease in vascular endothelial proteins—intercellular adhesion molecule 1 and vascular cell adhesion molecule 1—with a coincident reduction in the dermal lymphocytic infiltrate in treated lesions.¹¹ These results offer a somewhat satisfying view on the correlation between the theory and basic science of laser therapy and the subsequent clinical benefits afforded by laser treatment. A case series provided further evidence that PDL or intense pulsed light can ameliorate the cutaneous lesions of DLE in 16 patients in whom all other treatments had failed.¹²

Several other inflammatory dermatoses can be treated with PDL, though the evidence for most of these conditions is sporadic at best, consisting mostly of case reports and a few case series. Granuloma faciale is one such condition, with evidence of efficacy of the PDL dating back as far as 1999,¹³ though a more recent case series of 4 patients only showed response in 2 patients.¹⁴ Because granuloma faciale features vasculitis as a prominent feature in its pathology, targeting the blood vessels may be helpful, but it is important to remember that there is a complex interplay between multiple factors. For example, treatment with typical fluences used in dermatology can be proinflammatory, leading to tissue damage, necrosis, and posttreatment erythema. However, low-level laser therapy (LLLT) has been shown to downregulate proinflammatory mediators.¹⁵ Additionally, the presence of a large burden of inflammatory cells also may alter the effectiveness of the laser. Several case reports also the show effectiveness of both PDL and the CO₂ laser in treating lesions of cutaneous sarcoidosis, especially lupus pernio.^16-19 Of these 2 modalities, the use of the CO₂ laser for effective remodeling of lupus pernio may be more intuitive; however, it is still important to note that the mechanism of action of several of these laser modalities is unclear with regard to the clinical benefit shown. Morphea and scleroderma also have been treated with laser therapy. It is essential to understand that in many cases, laser therapy may be targeted to treat the precise cutaneous manifestations of disease in each individual patient (eg, CO₂ laser to treat disabling contractures and calcinosis cutis,^20,21 PDL to treat telangiectases related to morphea²²). Again, the most critical consideration is that the treatment modality should align with the cutaneous lesion being targeted.

A relatively recent development in the use of lasers has been LLLT, which refers to the use of lasers below levels where they would cause any thermal effects, thereby limiting tissue damage. Although the technology has existed for decades, there has been a recent flurry of reports extolling the many benefits of LLLT; however, the true physiologic effects of LLLT have yet to be determined, with many studies trying to elucidate its numerous effects on various signaling pathways, cell proliferation, and cellular respiration.^23-26 Upon reviewing the literature, the list of cutaneous conditions that are being treated with LLLT is vast, spanning acne, vitiligo, wounds, burns, psoriasis, and alopecia, among others.¹⁵ It is important to consider that the definition of LLLT in the literature is rather broad with a wide range of wavelengths, fluences, and power densities. As such, the specific laser settings and protocols may vary considerably among different practitioners and therefore the treatment results also may vary. Nevertheless, many studies have hinted at promising results in the use of LLLT in conditions that may have previously been extremely difficult to treat (eg, alopecia). Earlier trials had demonstrated a faster resolution time in patients with alopecia areata when LLLT was added to a topical regimen²⁷; however, the improvement was modest and lesions tended to improve with or without LLLT. Perhaps more compelling is the use of LLLT in treating androgenetic alopecia, a condition for which a satisfying facile treatment would truly carry great impact. Although physicians should be cautious of studies regarding LLLT and hair regrowth that are conducted by groups who may stand to benefit from producing such a device, the results are nonetheless notable, if only for the relative paucity of other therapeutic approaches toward this condition.^28,29 A randomized, double-blind, controlled, multicenter trial showed significant improvements in median hair thickness and density with LLLT (P=.01 and P=.003, respectively), though global appearance did not change significantly.³⁰

Laser Treatment of Skin Cancer

Lasers also have been used to treat cutaneous malignancies. Although they may be powerful in the treatment of these conditions, this treatment approach must be used with caution. As with any superficial treatment modality for skin cancer, it is difficult to ascertain if a lesion has been completely treated without any residual cancer cells, and therein lies the main caveat of laser treatment. With the use of a modality that causes a cutaneous response that may mask any underlying process, it is important to ensure that there is a reasonable degree of certainty that this treatment can effectively remove a cancerous lesion in its entirety while avoiding the theoretical risk that disturbing underlying vasculature and/or lymphatics may be modulating the ability of a cancer to metastasize. Thankfully, current evidence does not suggest that there are any downsides to laser treatment for malignancies. Clinically, we know that basal cell carcinomas (BCCs) often feature prominent vasculature, with telangiectases being used as a clinical marker to suggest the diagnosis of a BCC. Capitalizing on this aspect of the clinical lesion, PDL has been used to treat BCCs in 2 small studies with a response rate of approximately 75% for small BCCs in both studies.^31,32 A recent randomized controlled trial showed significant superiority of PDL as compared to the control (P<.0001) in treatment of BCC, with nearly 80% (44/56) of cases showing histologically proven complete remission at 6-month follow-up.³³ Thus, we have some promising data that suggest PDL may be a viable treatment option in BCC, especially in areas that are difficult to treat surgically.

Additionally, a newer treatment approach for BCC capitalizes on the ability of confocal microscopy to provide a feasible, bedside imaging modality to identify tumor margins. Confocal microscopy has been used as a road map to identify where and how to apply the laser treatment, thus allowing for a higher likelihood of complete destruction of the tumor, at least in theory.³⁴ Although the concept of using confocal microscopy to guide laser treatment of skin cancer has been shown in smaller proof-of-concept case series, it remains to be seen if it is not only an efficacious approach that may be widely adopted but also whether it is pragmatic to do so, as the equipment and expertise involved in using confocal microscopy is not trivial.

Finally, lasers also have been used in the treatment of mycosis fungoides (MF), or cutaneous T-cell lymphoma. It has been suggested that this modality is an excellent treatment option as a skin-directed therapy for stage IA or IB MFs limited to the acral surfaces or MF palmaris et plantaris.³⁵ The reasoning behind this approach was the effectiveness of narrowband UVB for early-stage MF, with an excimer laser operating at a similar wavelength (308 nm) and offering similar therapeutic benefits while limiting adverse effects to surrounding skin.³⁶ More recently, the excimer laser was applied to a small population of 6 patients, with 3 achieving complete response, 1 with partial response, 1 with stable disease, and 1 with progressive disease. The authors were careful to point out that the excimer laser should not be thought of as a replacement for narrowband UVB in early-stage MF but rather as an adjunctive treatment of specific targeted lesional areas.³⁶

Conclusion

Lasers are an important part of the dermatologist’s treatment arsenal. Although much attention has been focused on laser treatment for aesthetic indications, it is important not to overlook the fact that lasers also can be useful in the treatment of refractory skin diseases, as a first-line treatment in some conditions such as vascular lesions, or as an adjunctive treatment modality. There is a great deal of exciting research that may lead to new indications and a better understanding of how to best use these powerful tools, and the outlook is bright for the use of lasers in dermatology.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

Lichen striatus (LS) is a relatively rare and self-limited linear dermatosis of unknown etiology. Lichen striatus primarily affects children, with more than 50% of cases occurring in patients aged 5 to 15 years.^1,2 It presents clinically as a single unilateral linear band consisting of scaly, 1- to 3-mm papules that coalesce to form long streaks.^3,4 The diagnosis usually is made clinically based on the characteristic appearance of skin lesions and a pattern of distribution that follows the lines of Blaschko.^5,6 The papules usually are asymptomatic; however, if the patient is symptomatic, pruritus is the most common concern. Lichen striatus may resolve with postinflammatory hyperpigmentation or hypopigmentation that may last for several months to years.

Nail involvement is uncommon in LS; a review of the literature has shown that 30 cases have been reported in the world literature since 1941.⁷ Nail changes may present before, after, or concurrently with the skin lesions.^4,8 On rare occasions, nail involvement may be the only area of involvement without the presence of typical skin lesions.⁸ The involved nails may show longitudinal ridging, splitting, hyperkeratosis of the nail beds, thinning or thickening of the nail plate, nail pitting, and overcurvature of the nail plate, and rarely the nails may fall off completely.^8-10

We report the case of a boy who was diagnosed with isolated LS at 2 years of age. The lesions spontaneously resolved within 6 months. Three years later the patient presented with a rare manifestation of LS in the form of bilateral onychodystrophy.

Case Report

An otherwise healthy 2-year-old boy presented for evaluation of a nonpruritic linear rash on the right lower side of the abdomen of 3 weeks’ duration. A review of systems was negative for any other constitutional signs or symptoms. No sick contacts were reported at the patient’s home, and his immunizations were up-to-date. His medical history was remarkable for a burn on the left hand from contact with a hot object at 11 months of age that required skin grafting.

Dermatologic examination revealed a linear band of small, 1- to 3-mm, flesh-colored lichenoid papules. Many of the papules had a scaly appearance and some had a vesicular component or were flat topped. The band ranged from 2- to 3-cm wide and was 25 cm in length, extending from the right anterolateral part of the lower abdomen to the right upper lateral part of the buttocks (Figure 1). No abnormalities were noted on the rest of the skin. A diagnosis of LS was made.

Figure 1. A linear band of small, 1- to 3-mm, flesh-colored, lichenoid, scaly papules, some with a vesicular component. The band was 2- to 3-cm wide and 25-cm long, extending over the right side of the lower abdomen. Figure 2. Longitudinal ridging, splitting, and thinning of the proximal nail folds on the regrown nails. Figure 3. Bilateral pitting, thinning, and overcurvature of the nail plates of the toenails with more involvement of the toenails on the left foot.

At 5 years of age, the patient returned for evaluation of bluish discoloration and thinning of the nails of the left middle and ring fingers of several months duration. The patient was afebrile and appeared to be healthy. There was no lymphadenopathy or hepatomegaly and the rest of the physical examination by a pediatrician was unremarkable. The nails of the 2 affected fingers had fallen off 2 months prior to presentation and had started to regrow. On dermatologic examination, it was noted that the regrown nails showed some residual longitudinal ridging, thinning, and dark discoloration of the proximal nail folds (Figure 2). On examination of the other toenails and fingernails there was evidence of bilateral pitting, ridging, and discoloration (Figure 3). The left great toenail was predominantly affected. The patient’s guardians were not aware of the toenail changes and denied any history of trauma to the fingers. When asked about the course of the prior abdominal linear rash, they reported that the lesions had completely resolved within 6 months. The rare diagnosis of isolated onychodystrophy as a late manifestation of the prior LS was made.

Comment

The etiology of LS remains unknown, but there have been several hypotheses suggesting environmental triggers such as trauma¹¹ or infection.¹² Others have suggested a possible autoimmune response¹³ or genetic components.⁶ Reports of simultaneous occurrences of LS in siblings as well as in a mother and her son^14,15; outbreaks of LS among children who are not biologically related but in a shared living environment; and a possible seasonal variation suggest an environmental infectious agent (eg, a virus) as the possible triggering factor. However, laboratory testing for viral etiology in LS has not been helpful.

Many of the reported cases of LS have described a pattern of distribution along the lines of Blaschko.^5,6,16,17 Lines of Blaschko are thought to be embryologic in origin and caused by the segmental growth of clones of cutaneous cells or the mutation-induced mosaicism of cutaneous cells, which led to the theory that mosaicism is involved in LS. Lichen striatus needs to be differentiated from other conditions with similar cutaneous appearances (eg, lichen nitidus, linear lichen planus of the digits, linear psoriasis, linear keratosis follicularis, linear epidermal nevus).

Skin biopsy to confirm the diagnosis rarely is necessary, as LS is a self-limited disorder and generally no treatment is recommended. Topical and intralesional steroids do not routinely impact the resolution of LS; however, emollients and topical steroids may be used to treat associated dryness and pruritus, if present.¹⁸ Immunomodulators such as tacrolimus and pimecrolimus have been successfully used in treating persistent and pruritic LS lesions on the face and extremities.^19,20 Tacrolimus also has been successfully used to treat nail abnormalities in LS.²¹

Guardians and family members should be reassured that LS is a benign condition that generally resolves spontaneously within 3 to 12 months. Also, guardians should be counseled regarding the possibility of postinflammatory hyperpigmentation or hypopigmentation, which may last for several months to years, particularly in children with darker skin types. Lichen striatus of the nails may have a more protracted course, lasting from 6 months to 5 years,²² but usually resolves spontaneously and without deformity.

Our patient developed a rare case of isolated LS at 2 years of age. Reports have suggested later onset of the condition, with more than 50% of all LS cases occurring in children aged 5 to 15 years.^1,2 Despite the earlier onset in our case, the patient still presented with the classic nonpruritic single linear band of papules that is characteristic of LS.

The nail involvement in our case is quite intriguing because of its rarity, timing, and extent of involvement. Nail involvement is generally uncommon in LS, with approximately 30 cases reported worldwide since 1941.⁷ The nail changes in our patient were unique in their timing, with the isolated onychodystrophy developing 3 years after the initial skin lesion. This subtle timing may pose a diagnostic challenge in patients with LS if treating physicians are unable to link the presenting onychodystrophy to the earlier cutaneous component of the condition. Two reports have shown that nail changes in association with LS may occur at any time before, after, or concurrently with the skin lesions,^4,8 suggesting that on rare occasions, as in our case, nail involvement may be the only area of involvement without the presence of typical LS skin lesions.⁸

The nail involvement in our patient also showed a greater severity than prior reports,^8,9 as he lost 2 fingernails completely before regrowth. Also, the bilateral distribution of onychodystrophy in our patient involving both the fingernails and toenails appeared to be consistent with a report by Al-Niaimi and Cox.²²

Nail involvement in cases of LS may be underreported when, as in our case, nail dystrophy presents as the only area of involvement without the presence of the typical skin lesions characteristic of LS. It is reasonable to recommend that clinicians facing similar presentations of isolated onychodystrophy should include the possibility of LS in the differential diagnosis before committing patients to a more common diagnosis (eg, onychomycosis). Clinicians should inquire about any history of cutaneous LS and counsel patients to return for treatment should skin lesions develop that are suggestive of LS.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

To the Editor:
A 61-year-old woman with a history of atrial fibrillation, type 2 diabetes mellitus, and hyperlipidemia presented with an erythematous, edematous, pruritic eruption on the chest, neck, and arms of 2 weeks’ duration. The patient had no history of considerable sun exposure or reports of photosensitivity. One month prior to presentation she had started taking dronedarone for improved control of atrial fibrillation. She had no known history of drug allergies. Other medications included valsartan, digoxin, pioglitazone, simvastatin, aspirin, hydrocodone, and zolpidem, all of which were unchanged for years. There were no changes in topical products used.

Physical examination revealed confluent, well-demarcated, erythematous and edematous papules and plaques over the anterior aspect of the neck, bilateral forearms, and dorsal aspect of the hands, with a v-shaped distribution on the chest (Figure). There was notable sparing of the submental region, upper arms, abdomen, back, and legs. Dronedarone was discontinued and she was started on fluocinonide ointment 0.05% and oral hydroxyzine for pruritus. Her rash resolved within the following few weeks.

Confluent, well-demarcated, erythematous and edematous papules and plaques in a v-shaped distribution on the chest (A) and dorsal aspect of the hands (B).

Dronedarone is a noniodinated benzofuran derivative. It is structurally similar to and shares the antiarrhythmic properties of amiodarone,¹ and thus it is used in the treatment of atrial fibrillation and atrial flutter. However, the pulmonary and thyroid toxicities sometimes associated with amiodarone have not been observed with dronedarone. The primary side effect of dronedarone is gastrointestinal distress, specifically nausea, vomiting, and diarrhea. Dronedarone has been associated with severe liver injury and hepatic failure.² Cutaneous reactions appear to be an uncommon side effect of dronedarone therapy. Across 5 clinical studies (N=6285), adverse events involving skin and subcutaneous tissue including eczema, allergic dermatitis, pruritus, and nonspecific rash occurred in 5% of dronedarone and 3% of placebo patients. Photosensitivity reactions occurred in less than 1% of dronedarone recipients.³

Although the lack of a biopsy leaves the possibility of a contact or photocontact dermatitis, our patient demonstrated the potential for dronedarone to cause a photodistributed drug eruption that resolved after cessation of the medication.

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis

1. The risk for subsequently developing squamous cell carcinoma in situ of the vulva is most strongly associated with:

a. candidiasis

b. cicatricial pemphigoid

c. lichen planus

d. lichen sclerosus

e. recurrent Trichomonas infections

2. Vitamin D supplements and topical antibiotics commonly are used to treat:

a. desquamative inflammatory vaginitis

b. dysesthetic vulvodynia

c. human papillomavirus–related severe squamous dysplasia of the vulva and vagina

d. lichen sclerosus

e. psoriasis

3. A 28-year-old diabetic woman presented to your clinic with well-developed vulvar pruritus. She was known to have an implanted copper intrauterine device. A Papanicolaou test would most likely reveal:

a. bacteria

b. herpetic virocytes

c. high-grade dysplastic squamous cells

d. koilocytic squamous cells

e. pseudohyphae

4. A 54-year-old woman with Sjögren syndrome and atrophic gastritis presented to your clinic with vulvar pruritus. Atrophy of the skin and mucosa with fissures was clinically suggestive of:

a. candidiasis

b. dysesthetic vulvodynia

c. lichen sclerosus

d. lichen simplex chronicus

e. psoriasis

5. A 48-year-old woman was referred to your clinic for evaluation of persistent burning vulvar pain of 3 months’ duration. She said she felt tired most of the time. On physical examination the vulva looked normal. Commonly this condition is associated with:

a. diabetes mellitus

b. fibromyalgia

c. hypothyroidism

d. iron deficiency anemia

e. psoriasis