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The Diagnosis: Calcific Uremic Arteriolopathy

Computed tomography of the abdomen and pelvis with contrast revealed a right complex renal cyst with peripheral calcification; computed tomography of the head without contrast revealed atherosclerotic changes with calcification of the intracranial arteries, vertebral basilar arteries, and bilateral branches of the ophthalmic artery. Histopathology revealed occlusive vasculopathy with epidermal ischemic changes as well as dermal and subcutaneous vascular congestion and small thrombi. Within the subcutis, there were tiny stippled calcium deposits within very small vascular lumina (Figure). The combination of clinical and histological findings was highly suggestive of calcific uremic arteriolopathy, and the patient was transitioned to hemodialysis against a low-calcium bath to avoid hypercalcemia. Unfortunately, she developed complications related to sepsis and experienced worsening mentation. After a discussion with palliative care, the patient was transitioned to comfort measures and discharged home on hospice 1 week after the biopsy at her family’s request.

Calcific uremic arteriolopathy (also known as calciphylaxis) is a rare, life-threatening syndrome of widespread vascular calcification leading to microvascular occlusion within the dermis and subcutaneous tissues.¹ Clinically, it typically manifests as severely painful, purpuric skin lesions that evolve through phases of blistering, ulceration, and ultimately visible skin necrosis.² The pain likely is a consequence of ischemia and nociceptive activation and often may precede any visibly apparent skin lesions.³ Risk factors associated with the development of this condition include female sex; history of diabetes mellitus, obesity, rapid weight loss, or end-stage renal disease; abnormalities in calcium and phosphorus homeostasis; and vitamin K deficiency.^1,3 It is more prevalent in patients on peritoneal dialysis compared to hemodialysis.⁴

Calciphylaxis is diagnosed with combined clinical and histopathological evidence. Laboratory test abnormalities are not specific for disease; therefore, skin biopsy is the standard confirmatory test, though its practice is contentious due to the risk for nonhealing ulceration and increasing risk for infection.¹ Findings suggestive of disease include focal to diffuse calcification (intravascular, extravascular, or perieccrine), superficial fat calcium deposition, mid panniculus calcium deposition, mid panniculus vascular thrombi, and focal to diffuse angioplasia.⁵ The hallmark feature is diffuse calcification of small capillaries in adipose tissue.⁶

The mortality rate associated with this disease is high—a 6-month mortality rate of 27% to 43% has been reported from the time of diagnosis^7-9—which often is related to subsequent superimposed infections patients acquire from necrotic skin tissue.² The disease also carries high morbidity, with patients experiencing frequent hospitalizations related to pain, infections, and nonhealing wounds.⁶ There is no standard treatment, and trials have been limited to small sample sizes. A multidisciplinary treatment approach is essential to maximize outcomes, which includes wound care, risk factor modification, analgesia, and symptomatic management strategies.^1,2,6

Some pharmacologic agents have received noteworthy attention in treating calciphylaxis, including sodium thiosulfate (STS), bisphosphonates, and vitamin K supplementation.¹ The strongest evidence supporting the use of STS comes from 2 trials involving 53 and 27 dialysis patients, with complete remission in 14 (26%) and 14 (52%) patients, respectively.^10,11 However, these trials did not include control groups to compare outcomes, and mortality rates were similarly high among partial responders and nonresponders compared with patients not treated with STS. A 2018 systematic review failed to assess the efficacy of STS alone for the treatment of calciphylaxis but suggested there may be a future role for it, with 251 of 358 patients (70.1%) responding to therapy.¹²

Erythema ab igne is a cutaneous reaction related to long-term heat exposure, often from electronic devices such as laptops, heating pads, space heaters, or hot-water bottles.^13,14 Clinically, this rash appears as an erythematous, purpuric, or hyperpigmented reticular dermatosis that is below the clinical threshold to define a thermal burn.¹³ Lesions often are seen on the anterior thighs or across the abdomen.¹⁵ There usually are no long-term clinical sequelae; however, rare malignant transformation has been documented in cases of atrophy or nonhealing ulceration.¹⁶ Treatment is supportive with removal of the offending agent, but hyperpigmentation may persist for months to years.¹⁴

Livedo reticularis is a cutaneous pattern of mottled violaceous or hyperpigmented changes that often signifies underlying vascular dermal changes.¹⁷ It can be seen in various pathologic states, including vasculitis, autoimmune disease, connective tissue disease, neurologic disease, infection, or malignancy, or it can be drug induced.¹⁸ There are no pathognomonic microscopic changes, as the histology will drastically differ based on the etiology. Workup can be extensive; cues to the underlying pathology should be sought based on the patient’s history and concurrent presenting symptoms. Livedo reticularis is the most common dermatologic finding in patients with antiphospholipid syndrome, and workup should include antiphospholipid antibodies (eg, lupus anticoagulant, anticardiolipin, anti–beta-2-glycoproteins) as well as lupus testing (eg, antinuclear antibodies, anti– double-stranded DNA).¹⁹ Treatment is targeted at the underlying disease process.

Cryoglobulinemia is a disease characterized by abnormal serum immunoglobulins that precipitate at cold temperatures and is further subcategorized by the type of complexes that are deposited.²⁰ Type I represents purely monoclonal cryoglobulins, type III purely polyclonal, and type II a mixed picture. Clinical manifestations arise from excessive deposition of these proteins in the skin, joints, peripheral vasculature, and kidneys leading to purpuric skin lesions, chronic ulceration, arthralgia, and glomerulonephritis. Cutaneous findings may include erythematous to purpuric macular or papular changes with or without the presence of ulceration, infarction, or hemorrhagic crusting.²¹ Systemic disease often underlies a diagnosis, and further investigation for hepatitis C virus, connective tissue disease, and hematologic malignancies should be considered.²⁰ Treatment is targeted at underlying systemic disease, such as antiviral treatment for hepatitis or chemotherapeutic regimens for hematologic disease.²²

Polyarteritis nodosa is a systemic necrotizing vasculitis that typically involves small- to medium-sized arteries. Cutaneous manifestations often include subcutaneous nodules, livedo reticularis, and ulcerations most found on the lower extremities.²³ Systemic symptoms including fever, myalgia, arthralgia, and neuropathy often are present. Characteristic histopathology findings include inflammation and destruction of medium-sized arteries at the junctional zone of the dermis and subcutis along with microaneurysms along the vessels.²⁴ Treatment is based on the severity of disease, with localized cutaneous disease often being controlled with topical steroids and anti-inflammatory agents, while more widespread disease requires immunosuppression with systemic steroids, hydroxychloroquine, azathioprine, methotrexate, mycophenolate mofetil, or intravenous immunoglobulins.²³

The Diagnosis: Calcific Uremic Arteriolopathy

Computed tomography of the abdomen and pelvis with contrast revealed a right complex renal cyst with peripheral calcification; computed tomography of the head without contrast revealed atherosclerotic changes with calcification of the intracranial arteries, vertebral basilar arteries, and bilateral branches of the ophthalmic artery. Histopathology revealed occlusive vasculopathy with epidermal ischemic changes as well as dermal and subcutaneous vascular congestion and small thrombi. Within the subcutis, there were tiny stippled calcium deposits within very small vascular lumina (Figure). The combination of clinical and histological findings was highly suggestive of calcific uremic arteriolopathy, and the patient was transitioned to hemodialysis against a low-calcium bath to avoid hypercalcemia. Unfortunately, she developed complications related to sepsis and experienced worsening mentation. After a discussion with palliative care, the patient was transitioned to comfort measures and discharged home on hospice 1 week after the biopsy at her family’s request.

Calcific uremic arteriolopathy (also known as calciphylaxis) is a rare, life-threatening syndrome of widespread vascular calcification leading to microvascular occlusion within the dermis and subcutaneous tissues.¹ Clinically, it typically manifests as severely painful, purpuric skin lesions that evolve through phases of blistering, ulceration, and ultimately visible skin necrosis.² The pain likely is a consequence of ischemia and nociceptive activation and often may precede any visibly apparent skin lesions.³ Risk factors associated with the development of this condition include female sex; history of diabetes mellitus, obesity, rapid weight loss, or end-stage renal disease; abnormalities in calcium and phosphorus homeostasis; and vitamin K deficiency.^1,3 It is more prevalent in patients on peritoneal dialysis compared to hemodialysis.⁴

Calciphylaxis is diagnosed with combined clinical and histopathological evidence. Laboratory test abnormalities are not specific for disease; therefore, skin biopsy is the standard confirmatory test, though its practice is contentious due to the risk for nonhealing ulceration and increasing risk for infection.¹ Findings suggestive of disease include focal to diffuse calcification (intravascular, extravascular, or perieccrine), superficial fat calcium deposition, mid panniculus calcium deposition, mid panniculus vascular thrombi, and focal to diffuse angioplasia.⁵ The hallmark feature is diffuse calcification of small capillaries in adipose tissue.⁶

The mortality rate associated with this disease is high—a 6-month mortality rate of 27% to 43% has been reported from the time of diagnosis^7-9—which often is related to subsequent superimposed infections patients acquire from necrotic skin tissue.² The disease also carries high morbidity, with patients experiencing frequent hospitalizations related to pain, infections, and nonhealing wounds.⁶ There is no standard treatment, and trials have been limited to small sample sizes. A multidisciplinary treatment approach is essential to maximize outcomes, which includes wound care, risk factor modification, analgesia, and symptomatic management strategies.^1,2,6

Some pharmacologic agents have received noteworthy attention in treating calciphylaxis, including sodium thiosulfate (STS), bisphosphonates, and vitamin K supplementation.¹ The strongest evidence supporting the use of STS comes from 2 trials involving 53 and 27 dialysis patients, with complete remission in 14 (26%) and 14 (52%) patients, respectively.^10,11 However, these trials did not include control groups to compare outcomes, and mortality rates were similarly high among partial responders and nonresponders compared with patients not treated with STS. A 2018 systematic review failed to assess the efficacy of STS alone for the treatment of calciphylaxis but suggested there may be a future role for it, with 251 of 358 patients (70.1%) responding to therapy.¹²

Erythema ab igne is a cutaneous reaction related to long-term heat exposure, often from electronic devices such as laptops, heating pads, space heaters, or hot-water bottles.^13,14 Clinically, this rash appears as an erythematous, purpuric, or hyperpigmented reticular dermatosis that is below the clinical threshold to define a thermal burn.¹³ Lesions often are seen on the anterior thighs or across the abdomen.¹⁵ There usually are no long-term clinical sequelae; however, rare malignant transformation has been documented in cases of atrophy or nonhealing ulceration.¹⁶ Treatment is supportive with removal of the offending agent, but hyperpigmentation may persist for months to years.¹⁴

Livedo reticularis is a cutaneous pattern of mottled violaceous or hyperpigmented changes that often signifies underlying vascular dermal changes.¹⁷ It can be seen in various pathologic states, including vasculitis, autoimmune disease, connective tissue disease, neurologic disease, infection, or malignancy, or it can be drug induced.¹⁸ There are no pathognomonic microscopic changes, as the histology will drastically differ based on the etiology. Workup can be extensive; cues to the underlying pathology should be sought based on the patient’s history and concurrent presenting symptoms. Livedo reticularis is the most common dermatologic finding in patients with antiphospholipid syndrome, and workup should include antiphospholipid antibodies (eg, lupus anticoagulant, anticardiolipin, anti–beta-2-glycoproteins) as well as lupus testing (eg, antinuclear antibodies, anti– double-stranded DNA).¹⁹ Treatment is targeted at the underlying disease process.

Cryoglobulinemia is a disease characterized by abnormal serum immunoglobulins that precipitate at cold temperatures and is further subcategorized by the type of complexes that are deposited.²⁰ Type I represents purely monoclonal cryoglobulins, type III purely polyclonal, and type II a mixed picture. Clinical manifestations arise from excessive deposition of these proteins in the skin, joints, peripheral vasculature, and kidneys leading to purpuric skin lesions, chronic ulceration, arthralgia, and glomerulonephritis. Cutaneous findings may include erythematous to purpuric macular or papular changes with or without the presence of ulceration, infarction, or hemorrhagic crusting.²¹ Systemic disease often underlies a diagnosis, and further investigation for hepatitis C virus, connective tissue disease, and hematologic malignancies should be considered.²⁰ Treatment is targeted at underlying systemic disease, such as antiviral treatment for hepatitis or chemotherapeutic regimens for hematologic disease.²²

Polyarteritis nodosa is a systemic necrotizing vasculitis that typically involves small- to medium-sized arteries. Cutaneous manifestations often include subcutaneous nodules, livedo reticularis, and ulcerations most found on the lower extremities.²³ Systemic symptoms including fever, myalgia, arthralgia, and neuropathy often are present. Characteristic histopathology findings include inflammation and destruction of medium-sized arteries at the junctional zone of the dermis and subcutis along with microaneurysms along the vessels.²⁴ Treatment is based on the severity of disease, with localized cutaneous disease often being controlled with topical steroids and anti-inflammatory agents, while more widespread disease requires immunosuppression with systemic steroids, hydroxychloroquine, azathioprine, methotrexate, mycophenolate mofetil, or intravenous immunoglobulins.²³

The Diagnosis: Calcific Uremic Arteriolopathy

Computed tomography of the abdomen and pelvis with contrast revealed a right complex renal cyst with peripheral calcification; computed tomography of the head without contrast revealed atherosclerotic changes with calcification of the intracranial arteries, vertebral basilar arteries, and bilateral branches of the ophthalmic artery. Histopathology revealed occlusive vasculopathy with epidermal ischemic changes as well as dermal and subcutaneous vascular congestion and small thrombi. Within the subcutis, there were tiny stippled calcium deposits within very small vascular lumina (Figure). The combination of clinical and histological findings was highly suggestive of calcific uremic arteriolopathy, and the patient was transitioned to hemodialysis against a low-calcium bath to avoid hypercalcemia. Unfortunately, she developed complications related to sepsis and experienced worsening mentation. After a discussion with palliative care, the patient was transitioned to comfort measures and discharged home on hospice 1 week after the biopsy at her family’s request.

Calcific uremic arteriolopathy (also known as calciphylaxis) is a rare, life-threatening syndrome of widespread vascular calcification leading to microvascular occlusion within the dermis and subcutaneous tissues.¹ Clinically, it typically manifests as severely painful, purpuric skin lesions that evolve through phases of blistering, ulceration, and ultimately visible skin necrosis.² The pain likely is a consequence of ischemia and nociceptive activation and often may precede any visibly apparent skin lesions.³ Risk factors associated with the development of this condition include female sex; history of diabetes mellitus, obesity, rapid weight loss, or end-stage renal disease; abnormalities in calcium and phosphorus homeostasis; and vitamin K deficiency.^1,3 It is more prevalent in patients on peritoneal dialysis compared to hemodialysis.⁴

Calciphylaxis is diagnosed with combined clinical and histopathological evidence. Laboratory test abnormalities are not specific for disease; therefore, skin biopsy is the standard confirmatory test, though its practice is contentious due to the risk for nonhealing ulceration and increasing risk for infection.¹ Findings suggestive of disease include focal to diffuse calcification (intravascular, extravascular, or perieccrine), superficial fat calcium deposition, mid panniculus calcium deposition, mid panniculus vascular thrombi, and focal to diffuse angioplasia.⁵ The hallmark feature is diffuse calcification of small capillaries in adipose tissue.⁶

The mortality rate associated with this disease is high—a 6-month mortality rate of 27% to 43% has been reported from the time of diagnosis^7-9—which often is related to subsequent superimposed infections patients acquire from necrotic skin tissue.² The disease also carries high morbidity, with patients experiencing frequent hospitalizations related to pain, infections, and nonhealing wounds.⁶ There is no standard treatment, and trials have been limited to small sample sizes. A multidisciplinary treatment approach is essential to maximize outcomes, which includes wound care, risk factor modification, analgesia, and symptomatic management strategies.^1,2,6

Some pharmacologic agents have received noteworthy attention in treating calciphylaxis, including sodium thiosulfate (STS), bisphosphonates, and vitamin K supplementation.¹ The strongest evidence supporting the use of STS comes from 2 trials involving 53 and 27 dialysis patients, with complete remission in 14 (26%) and 14 (52%) patients, respectively.^10,11 However, these trials did not include control groups to compare outcomes, and mortality rates were similarly high among partial responders and nonresponders compared with patients not treated with STS. A 2018 systematic review failed to assess the efficacy of STS alone for the treatment of calciphylaxis but suggested there may be a future role for it, with 251 of 358 patients (70.1%) responding to therapy.¹²

Erythema ab igne is a cutaneous reaction related to long-term heat exposure, often from electronic devices such as laptops, heating pads, space heaters, or hot-water bottles.^13,14 Clinically, this rash appears as an erythematous, purpuric, or hyperpigmented reticular dermatosis that is below the clinical threshold to define a thermal burn.¹³ Lesions often are seen on the anterior thighs or across the abdomen.¹⁵ There usually are no long-term clinical sequelae; however, rare malignant transformation has been documented in cases of atrophy or nonhealing ulceration.¹⁶ Treatment is supportive with removal of the offending agent, but hyperpigmentation may persist for months to years.¹⁴

Livedo reticularis is a cutaneous pattern of mottled violaceous or hyperpigmented changes that often signifies underlying vascular dermal changes.¹⁷ It can be seen in various pathologic states, including vasculitis, autoimmune disease, connective tissue disease, neurologic disease, infection, or malignancy, or it can be drug induced.¹⁸ There are no pathognomonic microscopic changes, as the histology will drastically differ based on the etiology. Workup can be extensive; cues to the underlying pathology should be sought based on the patient’s history and concurrent presenting symptoms. Livedo reticularis is the most common dermatologic finding in patients with antiphospholipid syndrome, and workup should include antiphospholipid antibodies (eg, lupus anticoagulant, anticardiolipin, anti–beta-2-glycoproteins) as well as lupus testing (eg, antinuclear antibodies, anti– double-stranded DNA).¹⁹ Treatment is targeted at the underlying disease process.

Cryoglobulinemia is a disease characterized by abnormal serum immunoglobulins that precipitate at cold temperatures and is further subcategorized by the type of complexes that are deposited.²⁰ Type I represents purely monoclonal cryoglobulins, type III purely polyclonal, and type II a mixed picture. Clinical manifestations arise from excessive deposition of these proteins in the skin, joints, peripheral vasculature, and kidneys leading to purpuric skin lesions, chronic ulceration, arthralgia, and glomerulonephritis. Cutaneous findings may include erythematous to purpuric macular or papular changes with or without the presence of ulceration, infarction, or hemorrhagic crusting.²¹ Systemic disease often underlies a diagnosis, and further investigation for hepatitis C virus, connective tissue disease, and hematologic malignancies should be considered.²⁰ Treatment is targeted at underlying systemic disease, such as antiviral treatment for hepatitis or chemotherapeutic regimens for hematologic disease.²²

Polyarteritis nodosa is a systemic necrotizing vasculitis that typically involves small- to medium-sized arteries. Cutaneous manifestations often include subcutaneous nodules, livedo reticularis, and ulcerations most found on the lower extremities.²³ Systemic symptoms including fever, myalgia, arthralgia, and neuropathy often are present. Characteristic histopathology findings include inflammation and destruction of medium-sized arteries at the junctional zone of the dermis and subcutis along with microaneurysms along the vessels.²⁴ Treatment is based on the severity of disease, with localized cutaneous disease often being controlled with topical steroids and anti-inflammatory agents, while more widespread disease requires immunosuppression with systemic steroids, hydroxychloroquine, azathioprine, methotrexate, mycophenolate mofetil, or intravenous immunoglobulins.²³

The Diagnosis: Coral Dermatitis

At 3-week follow-up, the patient demonstrated remarkable improvement in the intensity and size of the erythematous cerebriform plaques following daily application of triamcinolone acetonide cream 0.1% (Figure). The lesion disappeared after several months and did not recur. The delayed presentation of symptoms with a history of incidental coral contact during snorkeling most likely represents the type IV hypersensitivity reaction seen in the diagnosis of coral dermatitis, an extraordinarily rare form of contact dermatitis.¹ Not all coral trigger skin reactions. Species of coral that contain nematocysts in their tentacles (aptly named stinging capsules) are responsible for the sting preceding coral dermatitis, as the nematocysts eject a coiled filament in response to human tactile stimulation that injects toxins into the epidermis.²

Acute, delayed, or chronic cutaneous changes follow envenomation. Acute responses arise immediately to a few hours after initial contact and are considered an irritant contact dermatitis.³ Local tissue histamine release and cascades of cytotoxic reactions often result in the characteristic urticarial or vesiculobullous plaques in addition to necrosis, piloerection, and localized lymphadenopathy.^2-4 Although relatively uncommon, there may be rapid onset of systemic symptoms such as fever, malaise, hives, nausea, or emesis. Cardiopulmonary events, hepatotoxicity, renal failure, or anaphylaxis are rare.² Histopathology of biopsy specimens reveals epidermal spongiosis with microvesicles and papillary dermal edema.^1,5 In comparison, delayed reactions occur within days to weeks and exhibit epidermal parakeratosis, spongiosis, basal layer vacuolization, focal necrosis, lymphocyte exocytosis, and papillary dermal edema with extravasated erythrocytes.1,6 Clinically, it may present as linear rows of erythematous papules with burning and pruritus.⁶ Chronic reactions manifest after months as difficult-to-treat, persistent lichenoid dermatitis occasionally accompanied by granulomatous changes.^1,2,4 Primary prevention measures after initial contact include an acetic acid rinse and cold compression to wash away residual nematocysts in the affected area.^4,7,8 If a rash develops, topical steroids are the mainstay of treatment.^3,8

In tandem with toxic nematocysts, the rigid calcified bodies of coral provide an additional self-defense mechanism against human contact.^2,4 The irregular haphazard nature of coral may catch novice divers off guard and lead to laceration of a mispositioned limb, thereby increasing the risk for secondary infections due to the introduction of calcium carbonate and toxic mucinous deposits at the wound site, warranting antibiotic treatment.^2,4,7 Because tropical locales are home to other natural dangers that inflict disease and mimic early signs of coral dermatitis, reaching an accurate diagnosis can be difficult, particularly for lower limb lesions. In summary, the diagnosis of coral dermatitis can be rendered based on morphology of the lesion and clinical context (exposure to corals and delayed symptoms) as well as response to topical steroids.

The differential diagnosis includes accidental trauma. Variations in impact force and patient skin integrity lead to a number of possible cutaneous manifestations seen in accidental trauma,⁹ which includes contusions resulting from burst capillaries underneath intact skin, abrasions due to the superficial epidermis scuffing away, and lacerations caused by enough force to rip and split the skin, leaving subcutaneous tissue between the intact tissue.^9,10 Typically, the pattern of injury can provide hints to match what object or organism caused the wound.⁹ However, delayed response and worsening symptoms, as seen in coral dermatitis, would be unusual in accidental trauma unless it is complicated by secondary infection (infectious dermatitis), which does not respond to topical steroids and requires antibiotic treatment.

Another differential diagnosis includes cutaneous larva migrans, which infests domesticated and stray animals. For example, hookworm larvae propagate their eggs inside the intestines of their host before fecal-soil transmission in sandy locales.¹¹ Unexpecting beachgoers travel barefoot on this contaminated soil, offering ample opportunity for the parasite to burrow into the upper dermis.^11,12 The clinical presentation includes signs and symptoms of creeping eruption such as pruritic, linear, serpiginous tracks. Topical treatment with thiabendazole requires application 3 times daily for 15 days, which increases the risk for nonadherence, yet this therapy proves advantageous if a patient does not tolerate oral agents due to systemic adverse effects.^11,12 Oral agents (eg, ivermectin, albendazole) offer improved adherence with a single dose^11,13; the cure rate was higher with a single dose of ivermectin 12 mg vs a single dose of albendazole 400 mg.13 The current suggested treatment is ivermectin 200 μg/kg by mouth daily for 1 or 2 days.¹⁴

The incidence of seabather’s eruption (also known as chinkui dermatitis) is highest during the summer season and fluctuates between epidemic and nonepidemic years.^15,16 It occurs sporadically worldwide mostly in tropical climates due to trapping of larvae spawn of sea animals such as crustaceans in swimwear. Initially, it presents as a pruritic and burning sensation after exiting the water, manifesting as a macular, papular, or maculopapular rash on areas covered by the swimsuit.^15,16 The sensation is worse in areas that are tightly banded on the swimsuit, including the waistband and elastic straps.¹⁵ Commonly, the affected individual will seek relief via a shower, which intensifies the burning, especially if the swimsuit has not been removed. The contaminated swimwear should be immediately discarded, as the trapped sea larvae’s nematocysts activate with the pressure and friction of movement.¹⁵ Seabather’s eruption typically resolves spontaneously within a week, but symptom management can be achieved with topical steroids (triamcinolone 0.1% or clobetasol 0.05%).^15,16 Unlike coral dermatitis, in seabather’s eruption the symptoms are immediate and the location of the eruption coincides with areas covered by the swimsuit.

The Diagnosis: Coral Dermatitis

At 3-week follow-up, the patient demonstrated remarkable improvement in the intensity and size of the erythematous cerebriform plaques following daily application of triamcinolone acetonide cream 0.1% (Figure). The lesion disappeared after several months and did not recur. The delayed presentation of symptoms with a history of incidental coral contact during snorkeling most likely represents the type IV hypersensitivity reaction seen in the diagnosis of coral dermatitis, an extraordinarily rare form of contact dermatitis.¹ Not all coral trigger skin reactions. Species of coral that contain nematocysts in their tentacles (aptly named stinging capsules) are responsible for the sting preceding coral dermatitis, as the nematocysts eject a coiled filament in response to human tactile stimulation that injects toxins into the epidermis.²

Acute, delayed, or chronic cutaneous changes follow envenomation. Acute responses arise immediately to a few hours after initial contact and are considered an irritant contact dermatitis.³ Local tissue histamine release and cascades of cytotoxic reactions often result in the characteristic urticarial or vesiculobullous plaques in addition to necrosis, piloerection, and localized lymphadenopathy.^2-4 Although relatively uncommon, there may be rapid onset of systemic symptoms such as fever, malaise, hives, nausea, or emesis. Cardiopulmonary events, hepatotoxicity, renal failure, or anaphylaxis are rare.² Histopathology of biopsy specimens reveals epidermal spongiosis with microvesicles and papillary dermal edema.^1,5 In comparison, delayed reactions occur within days to weeks and exhibit epidermal parakeratosis, spongiosis, basal layer vacuolization, focal necrosis, lymphocyte exocytosis, and papillary dermal edema with extravasated erythrocytes.1,6 Clinically, it may present as linear rows of erythematous papules with burning and pruritus.⁶ Chronic reactions manifest after months as difficult-to-treat, persistent lichenoid dermatitis occasionally accompanied by granulomatous changes.^1,2,4 Primary prevention measures after initial contact include an acetic acid rinse and cold compression to wash away residual nematocysts in the affected area.^4,7,8 If a rash develops, topical steroids are the mainstay of treatment.^3,8

In tandem with toxic nematocysts, the rigid calcified bodies of coral provide an additional self-defense mechanism against human contact.^2,4 The irregular haphazard nature of coral may catch novice divers off guard and lead to laceration of a mispositioned limb, thereby increasing the risk for secondary infections due to the introduction of calcium carbonate and toxic mucinous deposits at the wound site, warranting antibiotic treatment.^2,4,7 Because tropical locales are home to other natural dangers that inflict disease and mimic early signs of coral dermatitis, reaching an accurate diagnosis can be difficult, particularly for lower limb lesions. In summary, the diagnosis of coral dermatitis can be rendered based on morphology of the lesion and clinical context (exposure to corals and delayed symptoms) as well as response to topical steroids.

The differential diagnosis includes accidental trauma. Variations in impact force and patient skin integrity lead to a number of possible cutaneous manifestations seen in accidental trauma,⁹ which includes contusions resulting from burst capillaries underneath intact skin, abrasions due to the superficial epidermis scuffing away, and lacerations caused by enough force to rip and split the skin, leaving subcutaneous tissue between the intact tissue.^9,10 Typically, the pattern of injury can provide hints to match what object or organism caused the wound.⁹ However, delayed response and worsening symptoms, as seen in coral dermatitis, would be unusual in accidental trauma unless it is complicated by secondary infection (infectious dermatitis), which does not respond to topical steroids and requires antibiotic treatment.

Another differential diagnosis includes cutaneous larva migrans, which infests domesticated and stray animals. For example, hookworm larvae propagate their eggs inside the intestines of their host before fecal-soil transmission in sandy locales.¹¹ Unexpecting beachgoers travel barefoot on this contaminated soil, offering ample opportunity for the parasite to burrow into the upper dermis.^11,12 The clinical presentation includes signs and symptoms of creeping eruption such as pruritic, linear, serpiginous tracks. Topical treatment with thiabendazole requires application 3 times daily for 15 days, which increases the risk for nonadherence, yet this therapy proves advantageous if a patient does not tolerate oral agents due to systemic adverse effects.^11,12 Oral agents (eg, ivermectin, albendazole) offer improved adherence with a single dose^11,13; the cure rate was higher with a single dose of ivermectin 12 mg vs a single dose of albendazole 400 mg.13 The current suggested treatment is ivermectin 200 μg/kg by mouth daily for 1 or 2 days.¹⁴

The incidence of seabather’s eruption (also known as chinkui dermatitis) is highest during the summer season and fluctuates between epidemic and nonepidemic years.^15,16 It occurs sporadically worldwide mostly in tropical climates due to trapping of larvae spawn of sea animals such as crustaceans in swimwear. Initially, it presents as a pruritic and burning sensation after exiting the water, manifesting as a macular, papular, or maculopapular rash on areas covered by the swimsuit.^15,16 The sensation is worse in areas that are tightly banded on the swimsuit, including the waistband and elastic straps.¹⁵ Commonly, the affected individual will seek relief via a shower, which intensifies the burning, especially if the swimsuit has not been removed. The contaminated swimwear should be immediately discarded, as the trapped sea larvae’s nematocysts activate with the pressure and friction of movement.¹⁵ Seabather’s eruption typically resolves spontaneously within a week, but symptom management can be achieved with topical steroids (triamcinolone 0.1% or clobetasol 0.05%).^15,16 Unlike coral dermatitis, in seabather’s eruption the symptoms are immediate and the location of the eruption coincides with areas covered by the swimsuit.

The Diagnosis: Coral Dermatitis

At 3-week follow-up, the patient demonstrated remarkable improvement in the intensity and size of the erythematous cerebriform plaques following daily application of triamcinolone acetonide cream 0.1% (Figure). The lesion disappeared after several months and did not recur. The delayed presentation of symptoms with a history of incidental coral contact during snorkeling most likely represents the type IV hypersensitivity reaction seen in the diagnosis of coral dermatitis, an extraordinarily rare form of contact dermatitis.¹ Not all coral trigger skin reactions. Species of coral that contain nematocysts in their tentacles (aptly named stinging capsules) are responsible for the sting preceding coral dermatitis, as the nematocysts eject a coiled filament in response to human tactile stimulation that injects toxins into the epidermis.²

Acute, delayed, or chronic cutaneous changes follow envenomation. Acute responses arise immediately to a few hours after initial contact and are considered an irritant contact dermatitis.³ Local tissue histamine release and cascades of cytotoxic reactions often result in the characteristic urticarial or vesiculobullous plaques in addition to necrosis, piloerection, and localized lymphadenopathy.^2-4 Although relatively uncommon, there may be rapid onset of systemic symptoms such as fever, malaise, hives, nausea, or emesis. Cardiopulmonary events, hepatotoxicity, renal failure, or anaphylaxis are rare.² Histopathology of biopsy specimens reveals epidermal spongiosis with microvesicles and papillary dermal edema.^1,5 In comparison, delayed reactions occur within days to weeks and exhibit epidermal parakeratosis, spongiosis, basal layer vacuolization, focal necrosis, lymphocyte exocytosis, and papillary dermal edema with extravasated erythrocytes.1,6 Clinically, it may present as linear rows of erythematous papules with burning and pruritus.⁶ Chronic reactions manifest after months as difficult-to-treat, persistent lichenoid dermatitis occasionally accompanied by granulomatous changes.^1,2,4 Primary prevention measures after initial contact include an acetic acid rinse and cold compression to wash away residual nematocysts in the affected area.^4,7,8 If a rash develops, topical steroids are the mainstay of treatment.^3,8

In tandem with toxic nematocysts, the rigid calcified bodies of coral provide an additional self-defense mechanism against human contact.^2,4 The irregular haphazard nature of coral may catch novice divers off guard and lead to laceration of a mispositioned limb, thereby increasing the risk for secondary infections due to the introduction of calcium carbonate and toxic mucinous deposits at the wound site, warranting antibiotic treatment.^2,4,7 Because tropical locales are home to other natural dangers that inflict disease and mimic early signs of coral dermatitis, reaching an accurate diagnosis can be difficult, particularly for lower limb lesions. In summary, the diagnosis of coral dermatitis can be rendered based on morphology of the lesion and clinical context (exposure to corals and delayed symptoms) as well as response to topical steroids.

The differential diagnosis includes accidental trauma. Variations in impact force and patient skin integrity lead to a number of possible cutaneous manifestations seen in accidental trauma,⁹ which includes contusions resulting from burst capillaries underneath intact skin, abrasions due to the superficial epidermis scuffing away, and lacerations caused by enough force to rip and split the skin, leaving subcutaneous tissue between the intact tissue.^9,10 Typically, the pattern of injury can provide hints to match what object or organism caused the wound.⁹ However, delayed response and worsening symptoms, as seen in coral dermatitis, would be unusual in accidental trauma unless it is complicated by secondary infection (infectious dermatitis), which does not respond to topical steroids and requires antibiotic treatment.

Another differential diagnosis includes cutaneous larva migrans, which infests domesticated and stray animals. For example, hookworm larvae propagate their eggs inside the intestines of their host before fecal-soil transmission in sandy locales.¹¹ Unexpecting beachgoers travel barefoot on this contaminated soil, offering ample opportunity for the parasite to burrow into the upper dermis.^11,12 The clinical presentation includes signs and symptoms of creeping eruption such as pruritic, linear, serpiginous tracks. Topical treatment with thiabendazole requires application 3 times daily for 15 days, which increases the risk for nonadherence, yet this therapy proves advantageous if a patient does not tolerate oral agents due to systemic adverse effects.^11,12 Oral agents (eg, ivermectin, albendazole) offer improved adherence with a single dose^11,13; the cure rate was higher with a single dose of ivermectin 12 mg vs a single dose of albendazole 400 mg.13 The current suggested treatment is ivermectin 200 μg/kg by mouth daily for 1 or 2 days.¹⁴

The incidence of seabather’s eruption (also known as chinkui dermatitis) is highest during the summer season and fluctuates between epidemic and nonepidemic years.^15,16 It occurs sporadically worldwide mostly in tropical climates due to trapping of larvae spawn of sea animals such as crustaceans in swimwear. Initially, it presents as a pruritic and burning sensation after exiting the water, manifesting as a macular, papular, or maculopapular rash on areas covered by the swimsuit.^15,16 The sensation is worse in areas that are tightly banded on the swimsuit, including the waistband and elastic straps.¹⁵ Commonly, the affected individual will seek relief via a shower, which intensifies the burning, especially if the swimsuit has not been removed. The contaminated swimwear should be immediately discarded, as the trapped sea larvae’s nematocysts activate with the pressure and friction of movement.¹⁵ Seabather’s eruption typically resolves spontaneously within a week, but symptom management can be achieved with topical steroids (triamcinolone 0.1% or clobetasol 0.05%).^15,16 Unlike coral dermatitis, in seabather’s eruption the symptoms are immediate and the location of the eruption coincides with areas covered by the swimsuit.

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

The Diagnosis: Cutaneous Mastocytosis

A shave skin biopsy from the right lateral breast and a punch skin biopsy from the right thigh showed similar histopathology. There were dermal predominantly perivascular aggregates of cells demonstrating basophilic granular cytoplasm and round to oval nuclei (Figure, A and B). These cells were highlighted by CD117 immunohistochemical stain (Figure, C), consistent with mastocytes. Additionally, occasional lymphocytes and rare eosinophils were noted. These histopathologic findings confirmed the diagnosis of cutaneous mastocytosis (CM). The patient’s complete blood cell count was within reference range, but serum tryptase was elevated at 15.7 μg/L (reference range, <11.0 μg/L), which prompted a bone marrow biopsy to rule out systemic mastocytosis (SM). The result showed normocellular bone marrow with no evidence of dysplasia or increased blasts, granuloma, lymphoproliferative disorder, or malignancy. Fluorescence in situ hybridization for PDGFRA (platelet-derived growth factor receptor alpha) and KIT mutation was negative. Because CM developed predominantly on the right breast where the patient previously had received radiation therapy, we concluded that this reaction was triggered by exposure to ionizing radiation.

Mastocytosis can be divided into 2 groups: CM and SM.¹ The histologic differential diagnosis of CM includes solitary mastocytoma, urticaria pigmentosa, telangiectasia macularis eruptiva perstans, and diffuse mastocytosis.² Clinicopathologic correlation is of crucial importance to render the final diagnosis in these disorders. Immunohistochemically, mast cells express CD177, CD5, CD68, tryptase, and chymase. Unlike normal mast cells, neoplastic cells express CD2 and/or CD25; CD25 is commonly expressed in cutaneous involvement by SM.²

Macdonald and Feiwel³ reported the first case of CM following ionizing radiation. Cutaneous mastocytosis is most common in female patients and presents with redbrown macules originating at the site of radiation therapy. Prior literature suggests that radiation-associated CM has a predilection for White patients⁴; however, our patient was Hispanic. It also is important to note that the presentation of this rash may differ in individuals with skin of color. In one case it spread beyond the radiation site.² Systemic mast call–mediated symptoms can occur in both CM and SM. The macules manifest as blanching with pressure.⁵ Typically these macules also are asymptomatic, though a positive Darier sign has been reported.^6,7 The interval between radiotherapy and CM has ranged from 3 to 24 months.²

Patients with CM should have a serum tryptase evaluation along with a complete blood cell count, serum biochemistry, and liver function tests. Elevated serum tryptase has a high positive predictive value for SM and should prompt a bone marrow biopsy. Our patient’s bone marrow biopsy results failed to establish SM; however, her serum tryptase levels will be carefully monitored going forward. At the time of publication, the skin macules were still persistent but not worsening or symptomatic.

Treatment is focused on symptomatic relief of cutaneous symptoms, if present; avoiding triggers of mast cell degranulation; and implementing the use of oral antihistamines and leukotriene antagonists as needed. Because our patient was completely asymptomatic, we did not recommend any topical or oral treatment. However, we do counsel patients on avoiding triggers of mast cell degranulation including nonsteroidal anti-inflammatory drugs, morphine and codeine derivatives, alcohol, certain anesthetics, and anticholinergic medications.⁸

Additional diagnoses were ruled out for the following reasons: Although lichen planus pigmentosus presents with ill-defined, oval, gray-brown macules, histopathology shows a bandlike lymphocytic infiltrate at the dermoepidermal junction. Solar lentiginosis is characterized by grouped tan macules in a sun-exposed distribution. A fixed drug eruption is a delayed hypersensitivity reaction, usually to an ingested medication, characterized by violaceous or hyperpigmented patches, with histopathology showing interface dermatitis with a lymphoeosinophilic infiltrate. Eruptive seborrheic keratoses can result from sunburn or dermatitis but does not show mastocytes on histopathology.⁸

In conclusion, dermatologists should be reminded of the rare possibility of CM when evaluating an atypical eruption in a prior radiation field.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

The Diagnosis: Argyria-Induced Azure Lunulae

Argyria is an acquired condition resulting from excessive exogenous exposure to silver with subsequent gastrointestinal absorption and pigmentary tissue deposition. Upon further questioning, our patient disclosed a lifetime history of colloidal silver use, both as a topical antiseptic agent and intraorally for aphthous ulcers. Silver has a predilection for granular deposition in stromal tissues and basement membranes with sparing of the epidermis, manifesting as progressive, permanent, blue to slate gray discoloration of sunexposed skin, mucous membranes, and nail beds.¹ The patient was advised to discontinue use of colloidal silver to avoid development of further pigmentary changes. The appearance of his nails remained unchanged in the months following initial presentation, as expected, since argyria pigmentation is not anticipated to reverse upon colloidal silver cessation.

Nail involvement may be an early presentation of generalized argyria or may be found in isolation, as seen in our patient. Early recognition and patient education are essential to minimize cumulative silver deposition. Although dyspigmentation may impact psychosocial well-being secondary to aesthetic concerns, there is limited research supporting adverse systemic effects of argyria confined to the nail beds. Similarly, the majority of generalized cases are not associated with systemic complications; however, potential toxicities, as described in isolated case reports without conclusive causal relationships, include nyctalopia, renal or hepatic toxicity, pulmonary fibrosis, and neuropsychiatric events.^1-6 Successful treatment of cutaneous argyria has been reported with the 1064-nm Q-switched Nd:YAG laser; however, there have been no reported treatments for nail bed involvement.⁷ Due to the absence of systemic symptoms, additional mucocutaneous dyspigmentation, or cosmetic concerns regarding nail bed lunulae discoloration in our patient, no further intervention was pursued, except for continued colloidal silver cessation.

The differential diagnosis of blue-gray nail bed dyspigmentation is broad and includes cyanosis secondary to cardiopulmonary disease, drug-induced dyspigmentation, Wilson disease, argyria, chrysiasis, hereditary acrolabial telangiectasia, and pseudomonal infection or chloronychia.^1,8,9 Etiologic insight may be provided from a thorough review of prescription and over-the-counter medications as well as careful attention to the distribution of dyspigmentation. Medications commonly associated with bluish nail bed dyspigmentation include antimalarials, amiodarone, minocycline, clofazimine, chlorpromazine/phenothiazines, and various chemotherapeutic drugs; our patient was not taking any of these.^1,9

Cyanotic nail bed dyspigmentation secondary to cardiopulmonary disease likely manifests with more diffuse nail bed dyspigmentation and is not confined solely to the lunulae. Only drug-induced dyspigmentation, classically due to phenolphthalein-containing laxatives; Wilson disease; and argyria have a tendency to spare the distal nail bed, which is a presentation termed azure lunulae.⁸ The toenails typically are spared in argyria, while toenail involvement is variable in Wilson disease, and additional systemic symptoms—including hepatic, ophthalmologic, and neuropsychiatric—as well as potential family history would be expected.⁸ Phenolphthalein is no longer available in over-the-counter laxatives, as it was formally banned by the US Food and Drug Administration in 1999 due to concerns of carcinogenicity.¹⁰

Hereditary acrolabial telangiectasia is a familial condition with autosomal-dominant inheritance that can manifest similarly to argyria with blue-gray discoloration of the proximal nail bed; however, this condition also would demonstrate involvement of the vermilion border and nipple areolae, often with associated telangiectasia and migraine headaches.¹¹

Chloronychia (also known as green nail syndrome) is an infection of the nail bed with Pseudomonas aeruginosa that more commonly presents with greenblack discoloration with variable involvement of the fingernails and toenails. Chloronychia, often with associated onycholysis, typically is found in individuals with repeated exposure to water, soaps, and detergents.¹² Our patient’s long-standing and unwavering nail bed appearance, involvement of all fingernail lunulae, lack of additional symptoms, and disclosed use of over-the-counter colloidal silver supported a clinical diagnosis of argyriainduced azure lunulae.

Argyria-induced azure lunulae secondary to colloidal silver exposure is an uncommon yet clinically significant cause of nail bed dyspigmentation. Prompt identification and cessation of the offending agent can prevent progression of mucocutaneous dyspigmentation and avoid potential long-term sequelae from systemic deposition.

The Diagnosis: Superior Vena Cava Syndrome

Computed tomography angiography of the chest confirmed a diagnosis of superior vena cava (SVC) syndrome due to external pressure of the indwelling catheter. Upon diagnosis, the left indwelling catheter was removed. Further testing to assess for a potential pulmonary embolism was negative. Resolution of the ectatic spider veins and patientreported intermittent facial swelling was achieved after catheter removal.

Superior vena cava syndrome occurs when the SVC is occluded due to extrinsic pressure or thrombosis. Although classically thought to be due to underlying bronchogenic carcinomas, all pathologies that cause compression of the SVC also can lead to vessel occlusion.¹ Superior vena cava syndrome initially can be detected on physical examination. The most prominent skin finding includes diffusely dilated blood vessels on the central chest wall, which indicate the presence of collateral blood vessels.¹ Imaging studies such as abdominal computed tomography can provide information on the etiology of the condition but are not required for diagnosis. Given the high correlation of SVC syndrome with underlying lung and mediastinal carcinomas, imaging was warranted in our patient. Imaging also can distinguish if the condition is due to external pressure or thrombosis.² For SVC syndrome due to thrombosis, endovascular therapy is first-line management; however, mechanical thrombectomy may be preferred in patients with absolute contraindication to thrombolytic agents.³ In the setting of increased external pressure on the SVC, treatment includes the removal of the source of pressure.⁴

In a case series including 78 patients, ports and indwelling catheters accounted for 71% of benign SVC cases.⁵ Our patient’s SVC syndrome most likely was due to the indwelling catheter pressing on the SVC. The goal of treatment is to address the underlying cause—whether it be pressure or thrombosis. In the setting of increased external pressure, treatment includes removal of the source of pressure from the SVC.⁴

Other differential diagnoses to consider for newonset ectatic vessels on the chest wall include generalized essential telangiectasia, scleroderma, poikiloderma vasculare atrophicans, and caput medusae. Generalized essential telangiectasia is characterized by red or pink dilated capillary blood vessels in a branch or lacelike pattern predominantly on the lower limbs. The eruption primarily is asymptomatic, though tingling or numbness may be reported.⁶ The diagnosis can be made with a punch biopsy, with histopathology showing dilated vessels in the dermis.⁷

Scleroderma is a connective tissue fibrosis disorder with variable clinical presentations. The systemic sclerosis subset can be divided into localized systemic sclerosis and diffuse systemic sclerosis. Physical examination reveals cutaneous sclerosis in various areas of the body. Localized systemic sclerosis includes sclerosis of the fingers and face, while diffuse systemic sclerosis is notable for progression to the arms, legs, and trunk.⁸ In addition to sclerosis, diffuse telangiectases also can be observed. Systemic sclerosis is a clinical diagnosis based on physical examination and laboratory studies to identify antibodies such as antinuclear antibodies.

Poikiloderma vasculare atrophicans is a variant of cutaneous T-cell lymphoma. The initial presentation is characterized by plaques of hypopigmentation and hyperpigmentation with atrophy and telangiectases. The lesions may be asymptomatic or mildly pruritic and classically involve the trunk and flexural areas.⁹ The diagnosis is made with skin biopsy and immunohistochemical studies, with findings reflective of mycosis fungoides.

Caput medusae (palm tree sign) is a cardinal feature of portal hypertension characterized by grossly dilated and engorged periumbilical veins. To shunt blood from the portal venous system, cutaneous collateral veins between the umbilical veins and abdominal wall veins are used, resulting in the appearance of engorged veins in the anterior abdominal wall.¹⁰ The diagnosis can be made with abdominal ultrasonography showing the direction of blood flow through abdominal vessels.

The Diagnosis: Superior Vena Cava Syndrome

Computed tomography angiography of the chest confirmed a diagnosis of superior vena cava (SVC) syndrome due to external pressure of the indwelling catheter. Upon diagnosis, the left indwelling catheter was removed. Further testing to assess for a potential pulmonary embolism was negative. Resolution of the ectatic spider veins and patientreported intermittent facial swelling was achieved after catheter removal.

Superior vena cava syndrome occurs when the SVC is occluded due to extrinsic pressure or thrombosis. Although classically thought to be due to underlying bronchogenic carcinomas, all pathologies that cause compression of the SVC also can lead to vessel occlusion.¹ Superior vena cava syndrome initially can be detected on physical examination. The most prominent skin finding includes diffusely dilated blood vessels on the central chest wall, which indicate the presence of collateral blood vessels.¹ Imaging studies such as abdominal computed tomography can provide information on the etiology of the condition but are not required for diagnosis. Given the high correlation of SVC syndrome with underlying lung and mediastinal carcinomas, imaging was warranted in our patient. Imaging also can distinguish if the condition is due to external pressure or thrombosis.² For SVC syndrome due to thrombosis, endovascular therapy is first-line management; however, mechanical thrombectomy may be preferred in patients with absolute contraindication to thrombolytic agents.³ In the setting of increased external pressure on the SVC, treatment includes the removal of the source of pressure.⁴

In a case series including 78 patients, ports and indwelling catheters accounted for 71% of benign SVC cases.⁵ Our patient’s SVC syndrome most likely was due to the indwelling catheter pressing on the SVC. The goal of treatment is to address the underlying cause—whether it be pressure or thrombosis. In the setting of increased external pressure, treatment includes removal of the source of pressure from the SVC.⁴

Other differential diagnoses to consider for newonset ectatic vessels on the chest wall include generalized essential telangiectasia, scleroderma, poikiloderma vasculare atrophicans, and caput medusae. Generalized essential telangiectasia is characterized by red or pink dilated capillary blood vessels in a branch or lacelike pattern predominantly on the lower limbs. The eruption primarily is asymptomatic, though tingling or numbness may be reported.⁶ The diagnosis can be made with a punch biopsy, with histopathology showing dilated vessels in the dermis.⁷

Scleroderma is a connective tissue fibrosis disorder with variable clinical presentations. The systemic sclerosis subset can be divided into localized systemic sclerosis and diffuse systemic sclerosis. Physical examination reveals cutaneous sclerosis in various areas of the body. Localized systemic sclerosis includes sclerosis of the fingers and face, while diffuse systemic sclerosis is notable for progression to the arms, legs, and trunk.⁸ In addition to sclerosis, diffuse telangiectases also can be observed. Systemic sclerosis is a clinical diagnosis based on physical examination and laboratory studies to identify antibodies such as antinuclear antibodies.

Poikiloderma vasculare atrophicans is a variant of cutaneous T-cell lymphoma. The initial presentation is characterized by plaques of hypopigmentation and hyperpigmentation with atrophy and telangiectases. The lesions may be asymptomatic or mildly pruritic and classically involve the trunk and flexural areas.⁹ The diagnosis is made with skin biopsy and immunohistochemical studies, with findings reflective of mycosis fungoides.

Caput medusae (palm tree sign) is a cardinal feature of portal hypertension characterized by grossly dilated and engorged periumbilical veins. To shunt blood from the portal venous system, cutaneous collateral veins between the umbilical veins and abdominal wall veins are used, resulting in the appearance of engorged veins in the anterior abdominal wall.¹⁰ The diagnosis can be made with abdominal ultrasonography showing the direction of blood flow through abdominal vessels.

The Diagnosis: Superior Vena Cava Syndrome

Computed tomography angiography of the chest confirmed a diagnosis of superior vena cava (SVC) syndrome due to external pressure of the indwelling catheter. Upon diagnosis, the left indwelling catheter was removed. Further testing to assess for a potential pulmonary embolism was negative. Resolution of the ectatic spider veins and patientreported intermittent facial swelling was achieved after catheter removal.

Superior vena cava syndrome occurs when the SVC is occluded due to extrinsic pressure or thrombosis. Although classically thought to be due to underlying bronchogenic carcinomas, all pathologies that cause compression of the SVC also can lead to vessel occlusion.¹ Superior vena cava syndrome initially can be detected on physical examination. The most prominent skin finding includes diffusely dilated blood vessels on the central chest wall, which indicate the presence of collateral blood vessels.¹ Imaging studies such as abdominal computed tomography can provide information on the etiology of the condition but are not required for diagnosis. Given the high correlation of SVC syndrome with underlying lung and mediastinal carcinomas, imaging was warranted in our patient. Imaging also can distinguish if the condition is due to external pressure or thrombosis.² For SVC syndrome due to thrombosis, endovascular therapy is first-line management; however, mechanical thrombectomy may be preferred in patients with absolute contraindication to thrombolytic agents.³ In the setting of increased external pressure on the SVC, treatment includes the removal of the source of pressure.⁴

In a case series including 78 patients, ports and indwelling catheters accounted for 71% of benign SVC cases.⁵ Our patient’s SVC syndrome most likely was due to the indwelling catheter pressing on the SVC. The goal of treatment is to address the underlying cause—whether it be pressure or thrombosis. In the setting of increased external pressure, treatment includes removal of the source of pressure from the SVC.⁴

Other differential diagnoses to consider for newonset ectatic vessels on the chest wall include generalized essential telangiectasia, scleroderma, poikiloderma vasculare atrophicans, and caput medusae. Generalized essential telangiectasia is characterized by red or pink dilated capillary blood vessels in a branch or lacelike pattern predominantly on the lower limbs. The eruption primarily is asymptomatic, though tingling or numbness may be reported.⁶ The diagnosis can be made with a punch biopsy, with histopathology showing dilated vessels in the dermis.⁷

Scleroderma is a connective tissue fibrosis disorder with variable clinical presentations. The systemic sclerosis subset can be divided into localized systemic sclerosis and diffuse systemic sclerosis. Physical examination reveals cutaneous sclerosis in various areas of the body. Localized systemic sclerosis includes sclerosis of the fingers and face, while diffuse systemic sclerosis is notable for progression to the arms, legs, and trunk.⁸ In addition to sclerosis, diffuse telangiectases also can be observed. Systemic sclerosis is a clinical diagnosis based on physical examination and laboratory studies to identify antibodies such as antinuclear antibodies.

Poikiloderma vasculare atrophicans is a variant of cutaneous T-cell lymphoma. The initial presentation is characterized by plaques of hypopigmentation and hyperpigmentation with atrophy and telangiectases. The lesions may be asymptomatic or mildly pruritic and classically involve the trunk and flexural areas.⁹ The diagnosis is made with skin biopsy and immunohistochemical studies, with findings reflective of mycosis fungoides.

Caput medusae (palm tree sign) is a cardinal feature of portal hypertension characterized by grossly dilated and engorged periumbilical veins. To shunt blood from the portal venous system, cutaneous collateral veins between the umbilical veins and abdominal wall veins are used, resulting in the appearance of engorged veins in the anterior abdominal wall.¹⁰ The diagnosis can be made with abdominal ultrasonography showing the direction of blood flow through abdominal vessels.

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Cutaneous Sarcoidosis

A biopsy of a plaque on the back confirmed cutaneous sarcoidosis (CS). A chest radiograph demonstrated hilar nodes, and a referral was placed for comanagement with a pulmonologist. Histopathology was critical in making the diagnosis, with well-circumscribed noncaseating granulomas present in the dermis. The granulomas in CS often are described as naked, as there are minimal lymphocytes present and plasma cells normally are absent.¹ Because the lungs are the most common site of involvement, a chest radiograph is necessary to examine for systemic sarcoidosis. Laboratory workup is used to evaluate for lymphopenia, hypercalcemia, elevated blood sedimentation rate, and elevated angiotensin- converting enzyme levels, which are common in systemic sarcoidosis.¹

Sarcoidosis is a multisystemic granulomatous disorder with an unknown etiology. It is believed to develop in genetically predisposed individuals as a reaction to unidentified antigens in the environment.¹ Helper T cells (T_H1) respond to these environmental antigens in those who are susceptible, which leads to the disease process, but paradoxically, even with the elevation of cellular immune activity at the sites of the granulomatous inflammation, the peripheral immune response in these patients is suppressed as shown by lymphopenia.²

Cutaneous sarcoidosis is found in approximately one-third of patients with systemic sarcoidosis but can occur without systemic involvement.^1,2 Sarcoidosis is reported worldwide and affects patients of all races and ethnicities, ages, and sexes but does have a higher prevalence among Black individuals in the United States, patients younger than 40 years (peak incidence, 20–29 years of age), and females.² In 80% of patients, CS occurs before systemic sarcoidosis develops, or they may develop simultaneously.¹

Cutaneous sarcoidosis has a wide range of clinical presentations that are classified as specific and nonspecific. Specific lesions in CS contain noncaseating granulomas while nonspecific lesions in CS appear as reactive processes.² The most common specific presentation of CS includes papules that are brown in pigmentation in lighter skin tones and red to violaceous in darker skin tones (Figure). The most common nonspecific skin manifestation is erythema nodosum, which represents a hypersensitivity reaction. Cutaneous sarcoidosis can appear as hypopigmented or hyperpigmented patches or plaques.¹

Treatments for CS vary based on the individual.¹ For milder and more localized cases, topical or intralesional steroids may be used. If systemic sarcoidosis is suspected or if there is diffuse involvement of the skin, systemic steroids, antimalarials (eg, hydroxychloroquine), low-dose methotrexate, minocycline, allopurinol, azathioprine, isotretinoin, tumor necrosis factor α inhibitors, or psoralen plus long-wave UVA radiation may be used. If systemic sarcoidosis is present, referral to a pulmonologist is recommended for co-management.¹

Cutaneous sarcoidosis is known as the “great imitator,” and there are multiple diseases to consider in the differential that are distinguished by the physical findings.¹ In our case of a middle-aged Black woman with indurated plaques, a few diagnoses to consider were psoriasis, discoid lupus erythematosus (DLE), mycosis fungoides (MF), and tinea infection.

Psoriasis is a common disease, and 90% of patients have chronic plaquelike disease with well-demarcated erythematous plaques that have a silver-gray scale and a positive Auspitz sign (also known as pinpoint bleeding).³ Plaques often are distributed on the trunk, limb extensors, and scalp, along with nail changes. Some patients also have joint pain, indicating psoriatic arthritis. The etiology of psoriasis is unknown, but it develops due to unrestrained keratinocyte proliferation and defective differentiation, which leads to histopathology showing regular acanthosis and papillary dermal ectasia with rouleaux. Mild cases typically are treated with topical steroids or vitamin D, while more severe cases are treated with methotrexate, cyclosporine, retinoids, or biologics.³

Discoid lupus erythematosus occurs 4 times more often in Black patients than in White patients. Clinically, DLE begins as well-defined, erythematous, scaly patches that expand with hyperpigmentation at the periphery and leave an atrophic, scarred, hypopigmented center.⁴ It typically is localized to the head and neck, but in cases where it disseminates elsewhere on the body, the risk for systemic lupus erythematosus increases from 1.2% to 28%.5 Histopathology of DLE shows vacuolar degeneration of the basal cell layer in the epidermis along with patchy lymphocytic infiltrate in the dermis. Treatments range from topical steroids for mild cases to antimalarial agents, retinoids, anti-inflammatory drugs, and calcineurin inhibitors for more severe cases.⁴

Although there are multiple types of cutaneous T-cell lymphoma, the most common is MF, which traditionally is nonaggressive. The typical patient with MF is older than 60 years and presents with indolent, ongoing, flat to minimally indurated patches or plaques that have cigarette paper scale. As MF progresses, some plaques grow into tumors and can become more aggressive. Histologically, MF changes based on its clinical stage, with the initial phase showing epidermotropic atypical lymphocytes and later phases showing less epitheliotropic, larger, atypical lymphocytes. The treatment algorithm varies depending on cutaneous T-cell lymphoma staging.⁶

Tinea infections are caused by dermatophytes. In prepubertal children, they predominantly appear as tinea corporis (on the body) or tinea capitis (on the scalp), but in adults they appear as tinea cruris (on the groin), tinea pedis (on the feet), or tinea unguium (on the nails).⁷ Tinea infections classically are known to appear as an annular patch with an active erythematous scaling border and central clearing. The patches can be pruritic. Potassium hydroxide preparation of a skin scraping is a quick test to use in the office; if the results are inconclusive, a culture may be required. Treatment depends on the location of the infection but typically involves either topical or oral antifungal agents.⁷

The Diagnosis: Gnathostomiasis

The biopsy demonstrated a dense, eosinophilic, granulomatous infiltrate surrounding sections of a parasite with skeletal muscle bundles and intestines containing a brush border and luminal debris (Figure), which was consistent with a diagnosis of gnathostomiasis. Upon further questioning, he revealed that while in Peru he frequently consumed ceviche, which is a dish typically made from fresh raw fish cured in lemon or lime juice. He subsequently was treated with oral ivermectin 0.2 mg/kg once daily for 2 days with no evidence of recurrence 12 months later.

Cutaneous gnathostomiasis is the most common manifestation of infection caused by the third-stage larvae of the genus Gnathostoma. The nematode is endemic to tropical and subtropical regions of Japan and Southeast Asia, particularly Thailand. The disease has been increasingly observed in Central and South America. Humans can become infected through ingestion of undercooked meats, particularly freshwater fish but also poultry, snakes, or frogs. Few cases have been reported in North America and Europe presumably due to more stringent regulations governing the sourcing and storage of fish for consumption.^1-3 Restaurants in endemic regions also may use cheaper local freshwater or brackish fish compared to restaurants in the West, which use more expensive saltwater fish that do not harbor Gnathostoma species.¹ There is a false belief among restauranteurs and consumers that the larvae can be reliably killed by marinating meat in citrus juice or with concurrent consumption of alcohol or hot spices.² Adequately cooking or freezing meat to 20 °C for 3 to 5 days are the only effective ways to ensure that the larvae are killed.^1-3

The parasite requires its natural definitive hosts—fish-eating mammals such as pigs, cats, and dogs—to complete its life cycle and reproduce. Humans are accidental hosts in whom the parasite fails to reach sexual maturity.^1-3 Consequently, symptoms commonly are due to the migration of only 1 larva, but occasionally infection with 2 or more has been observed.^1,4

Human infection initially may result in malaise, fever, anorexia, abdominal pain, nausea, vomiting, and diarrhea as the parasite migrates through the stomach, intestines, and liver. After 2 to 4 weeks, larvae may reach the skin where they most commonly create ill-defined, erythematous, indurated, round or oval plaques or nodules described as nodular migratory panniculitis. These lesions tend to develop on the trunk or arms and correspond to the location of the migrating worm.^1,3,5 The larvae have been observed to migrate at 1 cm/h.⁶ Symptoms often wax and wane, with individual nodules lasting approximately 1 to 2 weeks. Uniquely, larval migration can result in a trail of subcutaneous hemorrhage that is considered pathognomonic and helps to differentiate gnathostomiasis from other forms of parasitosis such as strongyloidiasis and sparganosis.^1,3 Larvae are highly motile and invasive, and they are capable of producing a wide range of symptoms affecting virtually any part of the body.^1,2 Depending on the anatomic location of the migrating worm, infection also may result in neurologic, gastrointestinal, pulmonary, or ocular symptoms.^1-3,7 Eosinophilia is common but can subside in the chronic stage, as seen in our patient.¹

The classic triad of intermittent migratory nodules, eosinophilia, and a history of travel to Southeast Asia or another endemic region should raise suspicion for gnathostomiasis.^1-3,5,7 Unfortunately, confirmatory testing such as Gnathostoma serology is not readily available in the United States, and available serologic tests demonstrate frequent false positives and incomplete crossreactivity.^1,2,8 Accordingly, the diagnosis most commonly is solidified by combining cardinal clinical features with histologic findings of a dense eosinophilic inflammatory infiltrate involving the dermis and hypodermis.^2,5 In one study, the larva itself was only found in 12 of 66 (18%) skin biopsy specimens from patients with gnathostomiasis.⁵ If the larva is detected within the sections, it ranges from 2.5 to 12.5 mm in length and 0.4 to 1.2 mm in width and can exhibit cuticular spines, intestinal cells, and characteristic large lateral chords.^1,5

The treatment of choice is surgical removal of the worm. Oral albendazole (400–800 mg/d for 21 days) also is considered a first-line treatment and results in clinical cure in approximately 90% of cases. Two doses of oral ivermectin (0.2 mg/kg) spaced 24 to 48 hours apart is an acceptable alternative with comparable efficacy.^1-3 Care should be taken if involvement of the central nervous system is suspected, as antihelminthic treatment theoretically could be deleterious due to an inflammatory response to the dying larvae.^1,2,9

In the differential diagnosis, loiasis can resemble gnathostomiasis, but the former is endemic to Africa.³ Cutaneous larva migrans most frequently is caused by hookworms from the genus Ancylostoma, which classically leads to superficial serpiginous linear plaques that migrate at a rate of several millimeters per day. However, the larvae are believed to lack the collagenase enzyme required to penetrate the epidermal basement membrane and thus are not capable of producing deep-seated nodules or visceral symptoms.³Strongyloidiasis (larva currens) generally exhibits a more linear morphology, and infection would result in positive Strongyloides serology.⁷ Erythema nodosum is a septal panniculitis that can be triggered by infection, pregnancy, medications, connective tissue diseases, inflammatory conditions, and underlying malignancy.¹⁰

The Diagnosis: Gnathostomiasis

The biopsy demonstrated a dense, eosinophilic, granulomatous infiltrate surrounding sections of a parasite with skeletal muscle bundles and intestines containing a brush border and luminal debris (Figure), which was consistent with a diagnosis of gnathostomiasis. Upon further questioning, he revealed that while in Peru he frequently consumed ceviche, which is a dish typically made from fresh raw fish cured in lemon or lime juice. He subsequently was treated with oral ivermectin 0.2 mg/kg once daily for 2 days with no evidence of recurrence 12 months later.

Cutaneous gnathostomiasis is the most common manifestation of infection caused by the third-stage larvae of the genus Gnathostoma. The nematode is endemic to tropical and subtropical regions of Japan and Southeast Asia, particularly Thailand. The disease has been increasingly observed in Central and South America. Humans can become infected through ingestion of undercooked meats, particularly freshwater fish but also poultry, snakes, or frogs. Few cases have been reported in North America and Europe presumably due to more stringent regulations governing the sourcing and storage of fish for consumption.^1-3 Restaurants in endemic regions also may use cheaper local freshwater or brackish fish compared to restaurants in the West, which use more expensive saltwater fish that do not harbor Gnathostoma species.¹ There is a false belief among restauranteurs and consumers that the larvae can be reliably killed by marinating meat in citrus juice or with concurrent consumption of alcohol or hot spices.² Adequately cooking or freezing meat to 20 °C for 3 to 5 days are the only effective ways to ensure that the larvae are killed.^1-3

The parasite requires its natural definitive hosts—fish-eating mammals such as pigs, cats, and dogs—to complete its life cycle and reproduce. Humans are accidental hosts in whom the parasite fails to reach sexual maturity.^1-3 Consequently, symptoms commonly are due to the migration of only 1 larva, but occasionally infection with 2 or more has been observed.^1,4

Human infection initially may result in malaise, fever, anorexia, abdominal pain, nausea, vomiting, and diarrhea as the parasite migrates through the stomach, intestines, and liver. After 2 to 4 weeks, larvae may reach the skin where they most commonly create ill-defined, erythematous, indurated, round or oval plaques or nodules described as nodular migratory panniculitis. These lesions tend to develop on the trunk or arms and correspond to the location of the migrating worm.^1,3,5 The larvae have been observed to migrate at 1 cm/h.⁶ Symptoms often wax and wane, with individual nodules lasting approximately 1 to 2 weeks. Uniquely, larval migration can result in a trail of subcutaneous hemorrhage that is considered pathognomonic and helps to differentiate gnathostomiasis from other forms of parasitosis such as strongyloidiasis and sparganosis.^1,3 Larvae are highly motile and invasive, and they are capable of producing a wide range of symptoms affecting virtually any part of the body.^1,2 Depending on the anatomic location of the migrating worm, infection also may result in neurologic, gastrointestinal, pulmonary, or ocular symptoms.^1-3,7 Eosinophilia is common but can subside in the chronic stage, as seen in our patient.¹

The classic triad of intermittent migratory nodules, eosinophilia, and a history of travel to Southeast Asia or another endemic region should raise suspicion for gnathostomiasis.^1-3,5,7 Unfortunately, confirmatory testing such as Gnathostoma serology is not readily available in the United States, and available serologic tests demonstrate frequent false positives and incomplete crossreactivity.^1,2,8 Accordingly, the diagnosis most commonly is solidified by combining cardinal clinical features with histologic findings of a dense eosinophilic inflammatory infiltrate involving the dermis and hypodermis.^2,5 In one study, the larva itself was only found in 12 of 66 (18%) skin biopsy specimens from patients with gnathostomiasis.⁵ If the larva is detected within the sections, it ranges from 2.5 to 12.5 mm in length and 0.4 to 1.2 mm in width and can exhibit cuticular spines, intestinal cells, and characteristic large lateral chords.^1,5

The treatment of choice is surgical removal of the worm. Oral albendazole (400–800 mg/d for 21 days) also is considered a first-line treatment and results in clinical cure in approximately 90% of cases. Two doses of oral ivermectin (0.2 mg/kg) spaced 24 to 48 hours apart is an acceptable alternative with comparable efficacy.^1-3 Care should be taken if involvement of the central nervous system is suspected, as antihelminthic treatment theoretically could be deleterious due to an inflammatory response to the dying larvae.^1,2,9

In the differential diagnosis, loiasis can resemble gnathostomiasis, but the former is endemic to Africa.³ Cutaneous larva migrans most frequently is caused by hookworms from the genus Ancylostoma, which classically leads to superficial serpiginous linear plaques that migrate at a rate of several millimeters per day. However, the larvae are believed to lack the collagenase enzyme required to penetrate the epidermal basement membrane and thus are not capable of producing deep-seated nodules or visceral symptoms.³Strongyloidiasis (larva currens) generally exhibits a more linear morphology, and infection would result in positive Strongyloides serology.⁷ Erythema nodosum is a septal panniculitis that can be triggered by infection, pregnancy, medications, connective tissue diseases, inflammatory conditions, and underlying malignancy.¹⁰

The Diagnosis: Gnathostomiasis

The biopsy demonstrated a dense, eosinophilic, granulomatous infiltrate surrounding sections of a parasite with skeletal muscle bundles and intestines containing a brush border and luminal debris (Figure), which was consistent with a diagnosis of gnathostomiasis. Upon further questioning, he revealed that while in Peru he frequently consumed ceviche, which is a dish typically made from fresh raw fish cured in lemon or lime juice. He subsequently was treated with oral ivermectin 0.2 mg/kg once daily for 2 days with no evidence of recurrence 12 months later.

Cutaneous gnathostomiasis is the most common manifestation of infection caused by the third-stage larvae of the genus Gnathostoma. The nematode is endemic to tropical and subtropical regions of Japan and Southeast Asia, particularly Thailand. The disease has been increasingly observed in Central and South America. Humans can become infected through ingestion of undercooked meats, particularly freshwater fish but also poultry, snakes, or frogs. Few cases have been reported in North America and Europe presumably due to more stringent regulations governing the sourcing and storage of fish for consumption.^1-3 Restaurants in endemic regions also may use cheaper local freshwater or brackish fish compared to restaurants in the West, which use more expensive saltwater fish that do not harbor Gnathostoma species.¹ There is a false belief among restauranteurs and consumers that the larvae can be reliably killed by marinating meat in citrus juice or with concurrent consumption of alcohol or hot spices.² Adequately cooking or freezing meat to 20 °C for 3 to 5 days are the only effective ways to ensure that the larvae are killed.^1-3

The parasite requires its natural definitive hosts—fish-eating mammals such as pigs, cats, and dogs—to complete its life cycle and reproduce. Humans are accidental hosts in whom the parasite fails to reach sexual maturity.^1-3 Consequently, symptoms commonly are due to the migration of only 1 larva, but occasionally infection with 2 or more has been observed.^1,4

Human infection initially may result in malaise, fever, anorexia, abdominal pain, nausea, vomiting, and diarrhea as the parasite migrates through the stomach, intestines, and liver. After 2 to 4 weeks, larvae may reach the skin where they most commonly create ill-defined, erythematous, indurated, round or oval plaques or nodules described as nodular migratory panniculitis. These lesions tend to develop on the trunk or arms and correspond to the location of the migrating worm.^1,3,5 The larvae have been observed to migrate at 1 cm/h.⁶ Symptoms often wax and wane, with individual nodules lasting approximately 1 to 2 weeks. Uniquely, larval migration can result in a trail of subcutaneous hemorrhage that is considered pathognomonic and helps to differentiate gnathostomiasis from other forms of parasitosis such as strongyloidiasis and sparganosis.^1,3 Larvae are highly motile and invasive, and they are capable of producing a wide range of symptoms affecting virtually any part of the body.^1,2 Depending on the anatomic location of the migrating worm, infection also may result in neurologic, gastrointestinal, pulmonary, or ocular symptoms.^1-3,7 Eosinophilia is common but can subside in the chronic stage, as seen in our patient.¹

The classic triad of intermittent migratory nodules, eosinophilia, and a history of travel to Southeast Asia or another endemic region should raise suspicion for gnathostomiasis.^1-3,5,7 Unfortunately, confirmatory testing such as Gnathostoma serology is not readily available in the United States, and available serologic tests demonstrate frequent false positives and incomplete crossreactivity.^1,2,8 Accordingly, the diagnosis most commonly is solidified by combining cardinal clinical features with histologic findings of a dense eosinophilic inflammatory infiltrate involving the dermis and hypodermis.^2,5 In one study, the larva itself was only found in 12 of 66 (18%) skin biopsy specimens from patients with gnathostomiasis.⁵ If the larva is detected within the sections, it ranges from 2.5 to 12.5 mm in length and 0.4 to 1.2 mm in width and can exhibit cuticular spines, intestinal cells, and characteristic large lateral chords.^1,5

The treatment of choice is surgical removal of the worm. Oral albendazole (400–800 mg/d for 21 days) also is considered a first-line treatment and results in clinical cure in approximately 90% of cases. Two doses of oral ivermectin (0.2 mg/kg) spaced 24 to 48 hours apart is an acceptable alternative with comparable efficacy.^1-3 Care should be taken if involvement of the central nervous system is suspected, as antihelminthic treatment theoretically could be deleterious due to an inflammatory response to the dying larvae.^1,2,9

In the differential diagnosis, loiasis can resemble gnathostomiasis, but the former is endemic to Africa.³ Cutaneous larva migrans most frequently is caused by hookworms from the genus Ancylostoma, which classically leads to superficial serpiginous linear plaques that migrate at a rate of several millimeters per day. However, the larvae are believed to lack the collagenase enzyme required to penetrate the epidermal basement membrane and thus are not capable of producing deep-seated nodules or visceral symptoms.³Strongyloidiasis (larva currens) generally exhibits a more linear morphology, and infection would result in positive Strongyloides serology.⁷ Erythema nodosum is a septal panniculitis that can be triggered by infection, pregnancy, medications, connective tissue diseases, inflammatory conditions, and underlying malignancy.¹⁰

The Diagnosis: Lichen Sclerosus

Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).

Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.¹ It is thought to be underdiagnosed and underreported.² Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.^3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.^3,5 Furthermore, LS involving the palms and soles is exceedingly rare.² Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.^3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.^1,6

Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.⁶ Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.¹ Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.⁶

The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.³ Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.⁷ Lichen planus is considered to be more pruritic³ than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.⁸

Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.⁶ Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.^3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.⁶

Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.¹⁰ Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.

Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.¹¹ Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.³

The Diagnosis: Lichen Sclerosus

Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).

Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.¹ It is thought to be underdiagnosed and underreported.² Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.^3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.^3,5 Furthermore, LS involving the palms and soles is exceedingly rare.² Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.^3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.^1,6

Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.⁶ Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.¹ Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.⁶

The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.³ Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.⁷ Lichen planus is considered to be more pruritic³ than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.⁸

Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.⁶ Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.^3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.⁶

Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.¹⁰ Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.

Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.¹¹ Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.³

The Diagnosis: Lichen Sclerosus

Histopathology revealed a thin epidermis with homogenization of the upper dermal collagen. By contrast, the lower dermis was sclerotic with patchy chronic dermal infiltrate (Figure). Ultimately, the patient’s clinical presentation and histopathologic findings led to a diagnosis of lichen sclerosus (LS).

Lichen sclerosus is a rare chronic inflammatory skin condition that typically is characterized by porcelainwhite atrophic plaques on the skin, most often involving the external female genitalia including the vulva and perianal area.¹ It is thought to be underdiagnosed and underreported.² Extragenital manifestations may occur, though some cases are characterized by concomitant genital involvement.^3,4 Our patient presented with palmoplantar distribution of plaques without genitalia involvement. Approximately 6% to 10% of patients with extragenital LS do not have genital involvement at the time of diagnosis.^3,5 Furthermore, LS involving the palms and soles is exceedingly rare.² Although extragenital LS may be asymptomatic, patients can experience debilitating pruritus; bullae with hemorrhage and erosion; plaque thickening with repeated excoriations; and painful fissuring, especially if lesions are in areas that are susceptible to friction or tension.^3,6 New lesions on previously unaffected skin also may develop secondary to trauma through the Koebner phenomenon.^1,6

Histologically, LS is characterized by epidermal hyperkeratosis accompanied by follicular plugging, epidermal atrophy with flattened rete ridges, vacuolization of the basal epidermis, marked edema in the superficial dermis (in early lesions) or homogenized collagen in the upper dermis (in established lesions), and a lymphohistiocytic infiltrate beneath the homogenized collagen. Although the pathogenesis of LS is unclear, purported etiologic factors from studies in genital disease include immune dysfunction, genetic predisposition, infection, and trauma.⁶ Lichen sclerosus is associated strongly with autoimmune diseases including alopecia areata, vitiligo, autoimmune thyroiditis, diabetes mellitus, and pernicious anemia, indicating its potential multifactorial etiology and linkage to T-lymphocyte dysfunction.¹ Early LS lesions often appear as flat-topped and slightly scaly, hypopigmented, white or mildly erythematous, polygonal papules that coalesce to form larger plaques with peripheral erythema. With time, the inflammation subsides, and lesions become porcelain-white with varying degrees of palpable sclerosis, resembling thin paperlike wrinkles indicative of epidermal atrophy.⁶

The differential diagnosis of LS includes lichen planus (LP), morphea, discoid lupus erythematosus (DLE), and vitiligo.³ Lesions of LP commonly are described as flat-topped, polygonal, pink-purple papules localized mostly along the volar wrists, shins, presacral area, and hands.⁷ Lichen planus is considered to be more pruritic³ than LS and can be further distinguished by biopsy through identifying a well-formed granular layer and numerous cytoid bodies. Unlike LS, LP is not characterized by basement membrane thickening or epidermal atrophy.⁸

Skin lesions seen in morphea may resemble the classic atrophic white lesions of extragenital LS; however, it is unclear if the appearance of LS-like lesions with morphea is a simultaneous occurrence of 2 separate disorders or the development of clinical findings resembling LS in lesions of morphea.⁶ Furthermore, morphea involves deep inflammation and sclerosis of the dermis that may extend into subcutaneous fat without follicular plugging of the epidermis.^3,9 In contrast, LS primarily affects the epidermis and dermis with the presence of epidermal follicular plugging.⁶

Lesions seen in DLE are characterized as well-defined, annular, erythematous patches and plaques followed by follicular hyperkeratosis with adherent scaling. Upon removal of the scale, follicle-sized keratotic spikes (carpet tacks) are present.¹⁰ Scaling of lesions and the carpet tack sign were absent in our patient. In addition, DLE typically reveals surrounding pigmentation and scarring over plaques,3 which were not observed in our patient.

Vitiligo commonly is associated with extragenital LS. As with LS, vitiligo can be explained by mechanisms of immune checkpoint inhibitor–induced cytotoxicity as well as perforin and granzyme-B expression.¹¹ Although vitiligo resembles the late hypopigmented lesions of extragenital LS, there are no plaques or surface changes, and a larger, more generalized area of the skin typically is involved.³

The Diagnosis: Carcinoma en Cuirasse

Histopathology demonstrated a cellular infiltrate filling the dermis with sparing of the papillary and superficial reticular dermis (Figure 1A). The cells were arranged in strands and cords that infiltrated between sclerotic collagen bundles. Cytomorphologically, the cells ranged from epithelioid with large vesicular nuclei and prominent nucleoli to cuboidal with hyperchromatic nuclei with irregular contours and a high nuclear to cytoplasmic ratio (Figure 1B). Occasional mitotic figures were identified, and cells demonstrated diffuse nuclear positivity for GATA-3 (Figure 1C); 55% of the cells demonstrated estrogen receptor positivity, and immunohistochemistry of progesterone receptors was negative. These findings confirmed our patient’s diagnosis of breast carcinoma en cuirasse (CeC) as the primary manifestation of metastatic invasive ductal carcinoma. Our patient was treated with intravenous chemotherapy and tamoxifen.

Histopathologic findings of morphea include thickened hyalinized collagen bundles and loss of adventitial fat.¹ A diagnosis of chronic radiation dermatitis was inconsistent with our patient’s medical history and biopsy results, as pathology should reveal hyalinized collagen or stellate radiation fibroblasts.^2,3 Nests of squamous epithelial cells with abundant eosinophilic cytoplasm and large vesicular nuclei were not seen, excluding squamous cell carcinoma as a possible diagnosis.⁴ Although sclerosing sweat duct carcinoma is characterized by infiltrating cords in sclerotic dermis, the cells were not arranged in ductlike structures 1– to 2–cell layers thick, excluding this diagnosis.⁵

Carcinoma en cuirasse—named for skin involvement that appears similar to the metal breastplate of a cuirassier—is a rare form of cutaneous metastasis that typically presents with extensive infiltrative plaques resulting in fibrosis of the skin and subcutaneous tissue.^6,7 Carcinoma en cuirasse most commonly metastasizes from the breast but also may represent metastases from the lungs, gastrointestinal tract, or genitourinary systems.⁸ In the setting of a primary breast malignancy, metastatic plaques of CeC tend to represent tumor recurrence following a mastectomy procedure; however, in rare cases CeC can present as the primary manifestation of breast cancer or as a result of untreated malignancy.^6,9 In our patient, CeC was the primary manifestation of metastatic invasive ductal carcinoma with additional paraneoplastic ichthyosis (Figure 2).

Carcinoma en cuirasse comprises 3% to 6% of cutaneous metastases originating from the breast.^10,11 Breast cancer is the most common primary neoplasm displaying extracutaneous metastasis, comprising 70% of all cutaneous metastases in females.¹¹ Cutaneous metastasis often indicates late stage of disease, portending a poor prognosis. In our patient, the cutaneous nodules were present for approximately 3 years prior to the diagnosis of stage IV invasive ductal cell carcinoma with metastasis to the skin and lungs. Prior to admission, she had not been diagnosed with breast cancer, thus no treatments had been administered. It is uncommon for CeC to present as the initial finding and without prior treatment of the underlying malignancy. The median length of survival after diagnosis of cutaneous metastasis from breast cancer is 13.8 months, with a 10-year survival rate of 3.1%.¹²

In addition to cutaneous metastasis, breast cancer also may present with paraneoplastic dermatoses such as ichthyosis.¹³ Ichthyosis is characterized by extreme dryness, flaking, thickening, and mild pruritus.¹⁴ It most commonly is an inherited condition, but it may be acquired due to malignancy. Acquired ichthyosis may manifest in systemic diseases including systemic lupus erythematosus, sarcoidosis, and hypothyroidism.15 Although acquired ichthyosis is rare, it has been reported in cases of internal malignancy, most commonly lymphoproliferative malignancies and less frequently carcinoma of the breasts, cervix, and lungs. Patients who acquire ichthyosis in association with malignancy usually present with late-stage disease.¹⁵ Our patient acquired ichthyosis 3 months prior to admission and had never experienced it previously. Although the exact mechanism for acquiring ichthyosis remains unknown, it is uncertain if ichthyosis associated with malignancy is paraneoplastic or a result of chemotherapy.^14,16 In this case, the patient had not yet started chemotherapy at the time of the ichthyosis diagnosis, suggesting a paraneoplastic etiology.

Carcinoma en cuirasse and paraneoplastic ichthyosis individually are extremely rare manifestations of breast cancer. Thus, it is even rarer for these conditions to present concurrently. Treatment options for CeC include chemotherapy, radiotherapy, hormonal antagonists, and snake venom.¹¹ Systemic chemotherapy targeting the histopathologic type of the primary tumor is the treatment of choice. Other treatment methods usually are chosen for late stages of disease progression.10 Paraneoplastic ichthyosis has been reported to show improvement with treatment of the underlying primary malignancy by surgical removal or chemotherapy.^14,17 Tamoxifen less commonly is used for systemic treatment of CeC, but one case in the literature reported favorable outcomes.¹⁸

We describe 2 rare cutaneous manifestations of breast cancer occurring concomitantly: CeC and paraneoplastic ichthyosis. The combination of clinical and pathologic findings presented in this case solidified the diagnosis of metastatic invasive ductal carcinoma. We aim to improve recognition of paraneoplastic skin findings to accelerate the process of effective and efficient treatment.

The Diagnosis: Carcinoma en Cuirasse

Histopathology demonstrated a cellular infiltrate filling the dermis with sparing of the papillary and superficial reticular dermis (Figure 1A). The cells were arranged in strands and cords that infiltrated between sclerotic collagen bundles. Cytomorphologically, the cells ranged from epithelioid with large vesicular nuclei and prominent nucleoli to cuboidal with hyperchromatic nuclei with irregular contours and a high nuclear to cytoplasmic ratio (Figure 1B). Occasional mitotic figures were identified, and cells demonstrated diffuse nuclear positivity for GATA-3 (Figure 1C); 55% of the cells demonstrated estrogen receptor positivity, and immunohistochemistry of progesterone receptors was negative. These findings confirmed our patient’s diagnosis of breast carcinoma en cuirasse (CeC) as the primary manifestation of metastatic invasive ductal carcinoma. Our patient was treated with intravenous chemotherapy and tamoxifen.

Histopathologic findings of morphea include thickened hyalinized collagen bundles and loss of adventitial fat.¹ A diagnosis of chronic radiation dermatitis was inconsistent with our patient’s medical history and biopsy results, as pathology should reveal hyalinized collagen or stellate radiation fibroblasts.^2,3 Nests of squamous epithelial cells with abundant eosinophilic cytoplasm and large vesicular nuclei were not seen, excluding squamous cell carcinoma as a possible diagnosis.⁴ Although sclerosing sweat duct carcinoma is characterized by infiltrating cords in sclerotic dermis, the cells were not arranged in ductlike structures 1– to 2–cell layers thick, excluding this diagnosis.⁵

Carcinoma en cuirasse—named for skin involvement that appears similar to the metal breastplate of a cuirassier—is a rare form of cutaneous metastasis that typically presents with extensive infiltrative plaques resulting in fibrosis of the skin and subcutaneous tissue.^6,7 Carcinoma en cuirasse most commonly metastasizes from the breast but also may represent metastases from the lungs, gastrointestinal tract, or genitourinary systems.⁸ In the setting of a primary breast malignancy, metastatic plaques of CeC tend to represent tumor recurrence following a mastectomy procedure; however, in rare cases CeC can present as the primary manifestation of breast cancer or as a result of untreated malignancy.^6,9 In our patient, CeC was the primary manifestation of metastatic invasive ductal carcinoma with additional paraneoplastic ichthyosis (Figure 2).

Carcinoma en cuirasse comprises 3% to 6% of cutaneous metastases originating from the breast.^10,11 Breast cancer is the most common primary neoplasm displaying extracutaneous metastasis, comprising 70% of all cutaneous metastases in females.¹¹ Cutaneous metastasis often indicates late stage of disease, portending a poor prognosis. In our patient, the cutaneous nodules were present for approximately 3 years prior to the diagnosis of stage IV invasive ductal cell carcinoma with metastasis to the skin and lungs. Prior to admission, she had not been diagnosed with breast cancer, thus no treatments had been administered. It is uncommon for CeC to present as the initial finding and without prior treatment of the underlying malignancy. The median length of survival after diagnosis of cutaneous metastasis from breast cancer is 13.8 months, with a 10-year survival rate of 3.1%.¹²

In addition to cutaneous metastasis, breast cancer also may present with paraneoplastic dermatoses such as ichthyosis.¹³ Ichthyosis is characterized by extreme dryness, flaking, thickening, and mild pruritus.¹⁴ It most commonly is an inherited condition, but it may be acquired due to malignancy. Acquired ichthyosis may manifest in systemic diseases including systemic lupus erythematosus, sarcoidosis, and hypothyroidism.15 Although acquired ichthyosis is rare, it has been reported in cases of internal malignancy, most commonly lymphoproliferative malignancies and less frequently carcinoma of the breasts, cervix, and lungs. Patients who acquire ichthyosis in association with malignancy usually present with late-stage disease.¹⁵ Our patient acquired ichthyosis 3 months prior to admission and had never experienced it previously. Although the exact mechanism for acquiring ichthyosis remains unknown, it is uncertain if ichthyosis associated with malignancy is paraneoplastic or a result of chemotherapy.^14,16 In this case, the patient had not yet started chemotherapy at the time of the ichthyosis diagnosis, suggesting a paraneoplastic etiology.

Carcinoma en cuirasse and paraneoplastic ichthyosis individually are extremely rare manifestations of breast cancer. Thus, it is even rarer for these conditions to present concurrently. Treatment options for CeC include chemotherapy, radiotherapy, hormonal antagonists, and snake venom.¹¹ Systemic chemotherapy targeting the histopathologic type of the primary tumor is the treatment of choice. Other treatment methods usually are chosen for late stages of disease progression.10 Paraneoplastic ichthyosis has been reported to show improvement with treatment of the underlying primary malignancy by surgical removal or chemotherapy.^14,17 Tamoxifen less commonly is used for systemic treatment of CeC, but one case in the literature reported favorable outcomes.¹⁸

We describe 2 rare cutaneous manifestations of breast cancer occurring concomitantly: CeC and paraneoplastic ichthyosis. The combination of clinical and pathologic findings presented in this case solidified the diagnosis of metastatic invasive ductal carcinoma. We aim to improve recognition of paraneoplastic skin findings to accelerate the process of effective and efficient treatment.

The Diagnosis: Carcinoma en Cuirasse

Histopathology demonstrated a cellular infiltrate filling the dermis with sparing of the papillary and superficial reticular dermis (Figure 1A). The cells were arranged in strands and cords that infiltrated between sclerotic collagen bundles. Cytomorphologically, the cells ranged from epithelioid with large vesicular nuclei and prominent nucleoli to cuboidal with hyperchromatic nuclei with irregular contours and a high nuclear to cytoplasmic ratio (Figure 1B). Occasional mitotic figures were identified, and cells demonstrated diffuse nuclear positivity for GATA-3 (Figure 1C); 55% of the cells demonstrated estrogen receptor positivity, and immunohistochemistry of progesterone receptors was negative. These findings confirmed our patient’s diagnosis of breast carcinoma en cuirasse (CeC) as the primary manifestation of metastatic invasive ductal carcinoma. Our patient was treated with intravenous chemotherapy and tamoxifen.

Histopathologic findings of morphea include thickened hyalinized collagen bundles and loss of adventitial fat.¹ A diagnosis of chronic radiation dermatitis was inconsistent with our patient’s medical history and biopsy results, as pathology should reveal hyalinized collagen or stellate radiation fibroblasts.^2,3 Nests of squamous epithelial cells with abundant eosinophilic cytoplasm and large vesicular nuclei were not seen, excluding squamous cell carcinoma as a possible diagnosis.⁴ Although sclerosing sweat duct carcinoma is characterized by infiltrating cords in sclerotic dermis, the cells were not arranged in ductlike structures 1– to 2–cell layers thick, excluding this diagnosis.⁵

Carcinoma en cuirasse—named for skin involvement that appears similar to the metal breastplate of a cuirassier—is a rare form of cutaneous metastasis that typically presents with extensive infiltrative plaques resulting in fibrosis of the skin and subcutaneous tissue.^6,7 Carcinoma en cuirasse most commonly metastasizes from the breast but also may represent metastases from the lungs, gastrointestinal tract, or genitourinary systems.⁸ In the setting of a primary breast malignancy, metastatic plaques of CeC tend to represent tumor recurrence following a mastectomy procedure; however, in rare cases CeC can present as the primary manifestation of breast cancer or as a result of untreated malignancy.^6,9 In our patient, CeC was the primary manifestation of metastatic invasive ductal carcinoma with additional paraneoplastic ichthyosis (Figure 2).

Carcinoma en cuirasse comprises 3% to 6% of cutaneous metastases originating from the breast.^10,11 Breast cancer is the most common primary neoplasm displaying extracutaneous metastasis, comprising 70% of all cutaneous metastases in females.¹¹ Cutaneous metastasis often indicates late stage of disease, portending a poor prognosis. In our patient, the cutaneous nodules were present for approximately 3 years prior to the diagnosis of stage IV invasive ductal cell carcinoma with metastasis to the skin and lungs. Prior to admission, she had not been diagnosed with breast cancer, thus no treatments had been administered. It is uncommon for CeC to present as the initial finding and without prior treatment of the underlying malignancy. The median length of survival after diagnosis of cutaneous metastasis from breast cancer is 13.8 months, with a 10-year survival rate of 3.1%.¹²

In addition to cutaneous metastasis, breast cancer also may present with paraneoplastic dermatoses such as ichthyosis.¹³ Ichthyosis is characterized by extreme dryness, flaking, thickening, and mild pruritus.¹⁴ It most commonly is an inherited condition, but it may be acquired due to malignancy. Acquired ichthyosis may manifest in systemic diseases including systemic lupus erythematosus, sarcoidosis, and hypothyroidism.15 Although acquired ichthyosis is rare, it has been reported in cases of internal malignancy, most commonly lymphoproliferative malignancies and less frequently carcinoma of the breasts, cervix, and lungs. Patients who acquire ichthyosis in association with malignancy usually present with late-stage disease.¹⁵ Our patient acquired ichthyosis 3 months prior to admission and had never experienced it previously. Although the exact mechanism for acquiring ichthyosis remains unknown, it is uncertain if ichthyosis associated with malignancy is paraneoplastic or a result of chemotherapy.^14,16 In this case, the patient had not yet started chemotherapy at the time of the ichthyosis diagnosis, suggesting a paraneoplastic etiology.

Carcinoma en cuirasse and paraneoplastic ichthyosis individually are extremely rare manifestations of breast cancer. Thus, it is even rarer for these conditions to present concurrently. Treatment options for CeC include chemotherapy, radiotherapy, hormonal antagonists, and snake venom.¹¹ Systemic chemotherapy targeting the histopathologic type of the primary tumor is the treatment of choice. Other treatment methods usually are chosen for late stages of disease progression.10 Paraneoplastic ichthyosis has been reported to show improvement with treatment of the underlying primary malignancy by surgical removal or chemotherapy.^14,17 Tamoxifen less commonly is used for systemic treatment of CeC, but one case in the literature reported favorable outcomes.¹⁸

We describe 2 rare cutaneous manifestations of breast cancer occurring concomitantly: CeC and paraneoplastic ichthyosis. The combination of clinical and pathologic findings presented in this case solidified the diagnosis of metastatic invasive ductal carcinoma. We aim to improve recognition of paraneoplastic skin findings to accelerate the process of effective and efficient treatment.

The Diagnosis: Giant Acrochordon

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.^1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.³ The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.² Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.⁴ In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).⁴

The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).¹ It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.

Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.⁵ Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.

Nodular melanomas usually are blue to black and grow rapidly over the course of several months.⁶ They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.

Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.¹ Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.

Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.⁷ Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.

The Diagnosis: Giant Acrochordon

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.^1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.³ The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.² Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.⁴ In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).⁴

The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).¹ It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.

Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.⁵ Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.

Nodular melanomas usually are blue to black and grow rapidly over the course of several months.⁶ They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.

Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.¹ Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.

Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.⁷ Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.

The Diagnosis: Giant Acrochordon

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon. Acrochordons (also known as fibroepithelial polyps or skin tags) are among the most commonly identified skin lesions and are believed to affect up to 46% of the general population.^1,2 These benign growths typically appear after middle age in men and women alike and are believed to be of ectodermal and mesenchymal origin.³ The most common locations include the axillae, neck, and inguinal folds. They generally are small, measuring only a few millimeters, and frequently present as multiple lesions that are called giant acrochordons when their size exceeds 5 cm in length.² Acrochordons are benign lesions with only rare reports of the presence of basal or squamous cell carcinoma within the lesion on pathology.⁴ In addition to being cosmetically unsightly, patients with acrochordons often report pruritus. These lesions are easily removed in an outpatient setting via snip excision, cryosurgery, or electrodesiccation. Once removed, recurrence is unlikely. Despite the prevalence of fibroepithelial polyps worldwide, reports of giant acrochordons are limited. The histopathology of giant acrochordons is similar to smaller acrochordons, with features including epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures (Figure).⁴

The differential diagnosis of giant acrochordon includes neurofibroma, nodular melanoma, squamous cell carcinoma, and giant condylomata acuminata (Buschke-Löwenstein tumor).¹ It is important to consider the clinical presentation and histopathologic findings to differentiate giant acrochordons from these other entities.

Neurofibromas typically present as multiple flesh-colored to brown nodules that invaginate into the skin when minimal external pressure is applied.⁵ Histopathology demonstrates a discrete, nonencapsulated, dermal collection of small nerve fibers and loosely arranged spindle cells. In contrast, giant acrochordons typically present as large, fleshcolored, pedunculated, verrucous tumors with a central stalk. Histopathology reveals epidermal acanthosis and a central core of fibrovascular tissue without adnexal structures.

Nodular melanomas usually are blue to black and grow rapidly over the course of several months.⁶ They have signs of hemorrhagic crust, and histopathology reveals atypical melanocytes, frequent mitoses, pleomorphic tumor cells, and irregular clumping of chromatin within the nuclei. Giant acrochordons are flesh colored, benign, and do not have these malignant features.

Squamous cell carcinoma often presents as an erythematous scaly patch or red plaque on sun-exposed areas of the skin.¹ Histopathology of squamous cell carcinoma shows atypical keratinocytes with an invasive growth pattern; giant acrochordon does not show keratinocytic atypia or invasive epidermal growth.

Giant condylomata acuminata (Buschke-Löwenstein tumor) is a locally destructive verrucous plaque that typically appears on the penis but can occur elsewhere in the anogenital region.⁷ Histopathologic features include epidermal hyperplasia, papillomatosis, and koilocytes. In contrast, giant acrochordons typically are located on the buttocks and do not present with these epidermal changes.

Based on the clinical and histologic findings, our patient was diagnosed with a giant acrochordon, a rare variant of the common skin lesion. Excisional removal was critical for both diagnostic and treatment purposes. By considering the clinical presentation and histopathologic features of other conditions in the differential, giant acrochordons can be distinguished from other similar entities. Diagnosis and prompt surgical removal are important for management of these neoplasms and prevention of misdiagnosis.