Quiz

The Diagnosis: Palmoplantar Lichen Planus

A skin biopsy from a lesion on the inner wrist showed an interface pattern with a dense bandlike infiltrate obscuring the dermoepidermal junction coupled with a superficial perivascular infiltrate (Figure). At higher magnification (×10), the histologic features included compact orthokeratosis, wedge-shaped hypergranulosis, vacuolar degeneration of the basal layer, basal dyskeratosis, a dense lymphohistiocytic infiltrate obscuring the basement membrane, and melanophages in the papillary dermis.

Lichen planus (LP) is a common inflammatory disease of the skin presenting with flat-topped, violaceous, polygonal papules with fine white lines (Wickham striae) on the surface. It is recognized and diagnosed clinically by its characteristic appearance. Common areas of LP presentation include the shins, inner thighs, genitalia, trunk, volar aspect of the wrists, and oral mucosa.

Palmoplantar LP can present as erythematous plaques, punctuate keratosis, diffuse keratoderma, or ulcerated lesions. The most common concern among patients with LP is pruritus. One-fourth of patients with LP may present with lesions on the palms and soles, but diffuse palmoplantar hyperkeratosis is rare.¹ Lesions typically heal in 1 to 8 months, with an average of 3 months. Palmoplantar LP recurs within 1 year after stopping treatment in one-third of patients.¹

The cause of LP is unknown, but the pathophysiology is beginning to be understood. Cytotoxic CD8+ T cells stimulate apoptosis of the keratinocytes. The induction of this mechanism may be due to a self-antigen in a genetically predisposed patient. The evidence for LP being an autoimmune disease is supported by the high female predominance and the association of LP with other autoimmune diseases.² Patients with LP have an increased chance of coexisting hepatitis C virus. In a cross-sectional study of 303 patients, Lodi et al³ found that approximately 20% of LP patients were hepatitis C virus seropositive.

Treatment options for LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive agents.⁴ Our patient initially was treated with oral cyclosporine 100 mg every morning and oral methotrexate at a dose of 7.5 mg weekly. She also was treated with clobetasol ointment 0.05%. After 3 months, cyclosporine was discontinued. Methotrexate was maintained. At 5 months’ followup there was marked improvement of both clinical and symptomatic concerns with only residual palmoplantar erythema.

The differential diagnosis for pruritic palmoplantar hyperkeratosis is large. The most common differential diagnoses include hyperkeratotic eczema, psoriasis, secondary syphilis, and hereditary palmoplantar keratoderma. Lichen planus should be considered in the differential diagnosis of palmoplantar hyperkeratosis. A skin biopsy may be needed, as palmoplantar LP often has an atypical presentation.⁵

The Diagnosis: Palmoplantar Lichen Planus

A skin biopsy from a lesion on the inner wrist showed an interface pattern with a dense bandlike infiltrate obscuring the dermoepidermal junction coupled with a superficial perivascular infiltrate (Figure). At higher magnification (×10), the histologic features included compact orthokeratosis, wedge-shaped hypergranulosis, vacuolar degeneration of the basal layer, basal dyskeratosis, a dense lymphohistiocytic infiltrate obscuring the basement membrane, and melanophages in the papillary dermis.

Lichen planus (LP) is a common inflammatory disease of the skin presenting with flat-topped, violaceous, polygonal papules with fine white lines (Wickham striae) on the surface. It is recognized and diagnosed clinically by its characteristic appearance. Common areas of LP presentation include the shins, inner thighs, genitalia, trunk, volar aspect of the wrists, and oral mucosa.

Palmoplantar LP can present as erythematous plaques, punctuate keratosis, diffuse keratoderma, or ulcerated lesions. The most common concern among patients with LP is pruritus. One-fourth of patients with LP may present with lesions on the palms and soles, but diffuse palmoplantar hyperkeratosis is rare.¹ Lesions typically heal in 1 to 8 months, with an average of 3 months. Palmoplantar LP recurs within 1 year after stopping treatment in one-third of patients.¹

The cause of LP is unknown, but the pathophysiology is beginning to be understood. Cytotoxic CD8+ T cells stimulate apoptosis of the keratinocytes. The induction of this mechanism may be due to a self-antigen in a genetically predisposed patient. The evidence for LP being an autoimmune disease is supported by the high female predominance and the association of LP with other autoimmune diseases.² Patients with LP have an increased chance of coexisting hepatitis C virus. In a cross-sectional study of 303 patients, Lodi et al³ found that approximately 20% of LP patients were hepatitis C virus seropositive.

Treatment options for LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive agents.⁴ Our patient initially was treated with oral cyclosporine 100 mg every morning and oral methotrexate at a dose of 7.5 mg weekly. She also was treated with clobetasol ointment 0.05%. After 3 months, cyclosporine was discontinued. Methotrexate was maintained. At 5 months’ followup there was marked improvement of both clinical and symptomatic concerns with only residual palmoplantar erythema.

The differential diagnosis for pruritic palmoplantar hyperkeratosis is large. The most common differential diagnoses include hyperkeratotic eczema, psoriasis, secondary syphilis, and hereditary palmoplantar keratoderma. Lichen planus should be considered in the differential diagnosis of palmoplantar hyperkeratosis. A skin biopsy may be needed, as palmoplantar LP often has an atypical presentation.⁵

The Diagnosis: Palmoplantar Lichen Planus

A skin biopsy from a lesion on the inner wrist showed an interface pattern with a dense bandlike infiltrate obscuring the dermoepidermal junction coupled with a superficial perivascular infiltrate (Figure). At higher magnification (×10), the histologic features included compact orthokeratosis, wedge-shaped hypergranulosis, vacuolar degeneration of the basal layer, basal dyskeratosis, a dense lymphohistiocytic infiltrate obscuring the basement membrane, and melanophages in the papillary dermis.

Lichen planus (LP) is a common inflammatory disease of the skin presenting with flat-topped, violaceous, polygonal papules with fine white lines (Wickham striae) on the surface. It is recognized and diagnosed clinically by its characteristic appearance. Common areas of LP presentation include the shins, inner thighs, genitalia, trunk, volar aspect of the wrists, and oral mucosa.

Palmoplantar LP can present as erythematous plaques, punctuate keratosis, diffuse keratoderma, or ulcerated lesions. The most common concern among patients with LP is pruritus. One-fourth of patients with LP may present with lesions on the palms and soles, but diffuse palmoplantar hyperkeratosis is rare.¹ Lesions typically heal in 1 to 8 months, with an average of 3 months. Palmoplantar LP recurs within 1 year after stopping treatment in one-third of patients.¹

The cause of LP is unknown, but the pathophysiology is beginning to be understood. Cytotoxic CD8+ T cells stimulate apoptosis of the keratinocytes. The induction of this mechanism may be due to a self-antigen in a genetically predisposed patient. The evidence for LP being an autoimmune disease is supported by the high female predominance and the association of LP with other autoimmune diseases.² Patients with LP have an increased chance of coexisting hepatitis C virus. In a cross-sectional study of 303 patients, Lodi et al³ found that approximately 20% of LP patients were hepatitis C virus seropositive.

Treatment options for LP include topical and systemic steroids, tazarotene, acitretin, and immunosuppressive agents.⁴ Our patient initially was treated with oral cyclosporine 100 mg every morning and oral methotrexate at a dose of 7.5 mg weekly. She also was treated with clobetasol ointment 0.05%. After 3 months, cyclosporine was discontinued. Methotrexate was maintained. At 5 months’ followup there was marked improvement of both clinical and symptomatic concerns with only residual palmoplantar erythema.

The differential diagnosis for pruritic palmoplantar hyperkeratosis is large. The most common differential diagnoses include hyperkeratotic eczema, psoriasis, secondary syphilis, and hereditary palmoplantar keratoderma. Lichen planus should be considered in the differential diagnosis of palmoplantar hyperkeratosis. A skin biopsy may be needed, as palmoplantar LP often has an atypical presentation.⁵

The Diagnosis: Bilateral Auricular Tophaceous Gout

Histopathologic evaluation with hematoxylin and eosin staining demonstrated clusters of abundant granular amorphous material within the subcutaneous tissue (Figure 1). The overlying epidermis and dermis were unremarkable. The granular amorphous material demonstrated numerous monosodium urate crystals under polarized light (Figure 2). At a return visit following the biopsy results, the patient reported a history of a single episode of monoarticular gouty arthritis involving the right hallux approximately 6 months after the onset of the skin lesions. With the added clinical history and the biopsy results, his serum uric acid level was obtained and was found to be elevated at 9.2 mg/dL (reference range, 3.5–8 mg/dL).

In our patient, the clinical differential diagnosis included calcium deposits, weathering nodules, and tophaceous gout. The differential diagnosis of auricular lesions is broad, and benign lesions may mimic cancerous entities such as basal cell carcinoma and squamous cell carcinoma.¹ Therefore a detailed history, thorough physical examination, and tissue sampling are key to establishing the correct diagnosis. Our patient’s history of monoarticular gouty arthritis was only elucidated after a diagnosis of bilateral auricular tophaceous gout was made based on the biopsy results.

Subcutaneous tophi represent a chronic state of hyperuricemia and tend to manifest after long-standing polyarthritis and repeated acute gout attacks.^2-5 These lesions develop in approximately 50% of gout patients and usually occur an average of 11.6 years after the onset of disease.² There is a subset of individuals that are at higher risk for developing tophi, including elderly and female patients, diuretic and chronic nonsteroidal anti-inflammatory drug users, patients with a history of cyclosporine therapy, and patients with underlying chronic renal insufficiency.^2,6,7 The most commonly affected tissues are those with poor blood supply and lower temperatures, such as the ear helix and first metacarpal joint.⁴ The auricle is the most common site of tophi on the head and neck. Tophi of the helices are generally asymptomatic and nontender; however, tophi can become large, inflamed, and ulcerated, causing pressure and discomfort.² Combination treatment with dietary modification and antihyperuricemic therapy (eg, allopurinol) has been shown to reduce the size of lesions and prevent future tophi formation. However, these results may take months, warranting excision of large and symptomatic lesions.^4,8

Our case is unusual in that the onset of the auricular lesions predated the articular gout by 6 months. Gouty tophi as the initial presentation of hyperuricemia is rare; however, tophi formation without concomitant arthritis has been reported.^2,3,7,9 Wernick et al⁷ described 6 patients presenting with tophi before the onset of inflammatory arthritis that they attributed to changes in active inflammation by age (eg, elderly patients were more commonly immunosuppressed), chronic illnesses, and anti-inflammatory medications (eg, nonsteroidal anti-inflammatory drugs). Another possible explanation for this atypical presentation is misdiagnosis caused by other forms of arthritis (eg, rheumatoid arthritis, osteoarthritis) masking acute gout episodes. It also has been reported that monosodium urate crystals can be found in synovial fluid with no inflammation and therefore no symptoms.⁷

Tophi, although rare, may be the sole clinical manifestation of underlying gouty disease. It is important to be aware of this atypical presentation to prevent misdiagnosis and provide appropriate treatment.

The Diagnosis: Bilateral Auricular Tophaceous Gout

Histopathologic evaluation with hematoxylin and eosin staining demonstrated clusters of abundant granular amorphous material within the subcutaneous tissue (Figure 1). The overlying epidermis and dermis were unremarkable. The granular amorphous material demonstrated numerous monosodium urate crystals under polarized light (Figure 2). At a return visit following the biopsy results, the patient reported a history of a single episode of monoarticular gouty arthritis involving the right hallux approximately 6 months after the onset of the skin lesions. With the added clinical history and the biopsy results, his serum uric acid level was obtained and was found to be elevated at 9.2 mg/dL (reference range, 3.5–8 mg/dL).

In our patient, the clinical differential diagnosis included calcium deposits, weathering nodules, and tophaceous gout. The differential diagnosis of auricular lesions is broad, and benign lesions may mimic cancerous entities such as basal cell carcinoma and squamous cell carcinoma.¹ Therefore a detailed history, thorough physical examination, and tissue sampling are key to establishing the correct diagnosis. Our patient’s history of monoarticular gouty arthritis was only elucidated after a diagnosis of bilateral auricular tophaceous gout was made based on the biopsy results.

Subcutaneous tophi represent a chronic state of hyperuricemia and tend to manifest after long-standing polyarthritis and repeated acute gout attacks.^2-5 These lesions develop in approximately 50% of gout patients and usually occur an average of 11.6 years after the onset of disease.² There is a subset of individuals that are at higher risk for developing tophi, including elderly and female patients, diuretic and chronic nonsteroidal anti-inflammatory drug users, patients with a history of cyclosporine therapy, and patients with underlying chronic renal insufficiency.^2,6,7 The most commonly affected tissues are those with poor blood supply and lower temperatures, such as the ear helix and first metacarpal joint.⁴ The auricle is the most common site of tophi on the head and neck. Tophi of the helices are generally asymptomatic and nontender; however, tophi can become large, inflamed, and ulcerated, causing pressure and discomfort.² Combination treatment with dietary modification and antihyperuricemic therapy (eg, allopurinol) has been shown to reduce the size of lesions and prevent future tophi formation. However, these results may take months, warranting excision of large and symptomatic lesions.^4,8

Our case is unusual in that the onset of the auricular lesions predated the articular gout by 6 months. Gouty tophi as the initial presentation of hyperuricemia is rare; however, tophi formation without concomitant arthritis has been reported.^2,3,7,9 Wernick et al⁷ described 6 patients presenting with tophi before the onset of inflammatory arthritis that they attributed to changes in active inflammation by age (eg, elderly patients were more commonly immunosuppressed), chronic illnesses, and anti-inflammatory medications (eg, nonsteroidal anti-inflammatory drugs). Another possible explanation for this atypical presentation is misdiagnosis caused by other forms of arthritis (eg, rheumatoid arthritis, osteoarthritis) masking acute gout episodes. It also has been reported that monosodium urate crystals can be found in synovial fluid with no inflammation and therefore no symptoms.⁷

Tophi, although rare, may be the sole clinical manifestation of underlying gouty disease. It is important to be aware of this atypical presentation to prevent misdiagnosis and provide appropriate treatment.

The Diagnosis: Bilateral Auricular Tophaceous Gout

Histopathologic evaluation with hematoxylin and eosin staining demonstrated clusters of abundant granular amorphous material within the subcutaneous tissue (Figure 1). The overlying epidermis and dermis were unremarkable. The granular amorphous material demonstrated numerous monosodium urate crystals under polarized light (Figure 2). At a return visit following the biopsy results, the patient reported a history of a single episode of monoarticular gouty arthritis involving the right hallux approximately 6 months after the onset of the skin lesions. With the added clinical history and the biopsy results, his serum uric acid level was obtained and was found to be elevated at 9.2 mg/dL (reference range, 3.5–8 mg/dL).

In our patient, the clinical differential diagnosis included calcium deposits, weathering nodules, and tophaceous gout. The differential diagnosis of auricular lesions is broad, and benign lesions may mimic cancerous entities such as basal cell carcinoma and squamous cell carcinoma.¹ Therefore a detailed history, thorough physical examination, and tissue sampling are key to establishing the correct diagnosis. Our patient’s history of monoarticular gouty arthritis was only elucidated after a diagnosis of bilateral auricular tophaceous gout was made based on the biopsy results.

Subcutaneous tophi represent a chronic state of hyperuricemia and tend to manifest after long-standing polyarthritis and repeated acute gout attacks.^2-5 These lesions develop in approximately 50% of gout patients and usually occur an average of 11.6 years after the onset of disease.² There is a subset of individuals that are at higher risk for developing tophi, including elderly and female patients, diuretic and chronic nonsteroidal anti-inflammatory drug users, patients with a history of cyclosporine therapy, and patients with underlying chronic renal insufficiency.^2,6,7 The most commonly affected tissues are those with poor blood supply and lower temperatures, such as the ear helix and first metacarpal joint.⁴ The auricle is the most common site of tophi on the head and neck. Tophi of the helices are generally asymptomatic and nontender; however, tophi can become large, inflamed, and ulcerated, causing pressure and discomfort.² Combination treatment with dietary modification and antihyperuricemic therapy (eg, allopurinol) has been shown to reduce the size of lesions and prevent future tophi formation. However, these results may take months, warranting excision of large and symptomatic lesions.^4,8

Our case is unusual in that the onset of the auricular lesions predated the articular gout by 6 months. Gouty tophi as the initial presentation of hyperuricemia is rare; however, tophi formation without concomitant arthritis has been reported.^2,3,7,9 Wernick et al⁷ described 6 patients presenting with tophi before the onset of inflammatory arthritis that they attributed to changes in active inflammation by age (eg, elderly patients were more commonly immunosuppressed), chronic illnesses, and anti-inflammatory medications (eg, nonsteroidal anti-inflammatory drugs). Another possible explanation for this atypical presentation is misdiagnosis caused by other forms of arthritis (eg, rheumatoid arthritis, osteoarthritis) masking acute gout episodes. It also has been reported that monosodium urate crystals can be found in synovial fluid with no inflammation and therefore no symptoms.⁷

Tophi, although rare, may be the sole clinical manifestation of underlying gouty disease. It is important to be aware of this atypical presentation to prevent misdiagnosis and provide appropriate treatment.

The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

The Diagnosis: Acquired Acrodermatitis Enteropathica

Acquired acrodermatitis enteropathica (AAE) is a rare disorder caused by severe zinc deficiency. Although acrodermatitis enteropathica is an autosomal-recessive disorder that typically manifests in infancy, AAE also can result from poor zinc intake, impaired absorption, or accelerated losses. There are reports of AAE in patients with zinc-deficient diets,¹ eating disorders,² bariatric and other gastrointestinal surgeries,³ malabsorptive diseases,⁴ and nephrotic syndrome.⁵

Zinc plays an important role in DNA and RNA synthesis, reactive oxygen species attenuation, and energy metabolism, allowing for proper wound healing, skin differentiation, and proliferation.⁶ Zinc is found in most foods, but animal protein contains higher concentrations (Table).⁷ Approximately 85% of zinc is stored in muscles and bones, with only a small amount of accessible zinc available in the liver. Liver stores can be depleted as quickly as 1 week.⁸ Total parenteral nutrition without trace element supplementation can quickly predispose patients to AAE.

Diagnosis of this condition requires triangulation of clinical presentation, histopathology examination, and laboratory findings. Acrodermatitis enteropathica typically is characterized by dermatitis, diarrhea, and epidermal appendage findings. In its early stages, the dermatitis often manifests with angular cheilitis and paronychia.⁹ Patients then develop erythema, erosions, and occasionally vesicles or psoriasiform plaques in periorificial, perineal, and acral sites (Figure 1). Epidermal appendage effects include generalized alopecia and thinning nails with white transverse ridges. Although dermatologic and gastrointestinal manifestations are the most obvious, severe AAE may cause other symptoms, including mental slowing, hypogonadism, and impaired immune function.⁹

Histopathology of AAE skin lesions is similar to other nutritional deficiencies. Early changes are more specific to deficiency dermatitis and include cytoplasmic pallor and ballooning degeneration of keratinocytes in the stratum spinosum and granulosum.⁹ Necrolysis results in confluent keratinocyte necrosis developing into subcorneal bulla. Later in the disease course, the presentation becomes psoriasiform with keratinocyte dyskeratosis and confluent parakeratosis¹⁰ (Figure 2). Dermal edema with dilated tortuous vessels and a neutrophilic infiltrate may be present throughout disease progression.

Common laboratory abnormalities used to confirm zinc deficiency are decreased plasma zinc and alkaline phosphatase levels. Plasma zinc levels should be drawn after fasting because zinc levels decrease after food intake.⁹ Concurrent albumin levels should be drawn to correct for low levels caused by hypoalbuminemia. Acquired acrodermatitis enteropathica has been seen in patients with only mildly decreased plasma zinc levels or even zinc levels within reference range.¹¹ Alkaline phosphatase metalloenzyme synthesis requires zinc and a decreased level suggests zinc deficiency even with a plasma zinc level within reference range. Alkaline phosphatase levels usually can be ascertained in a matter of hours, while the zinc levels take much longer to result.

Acquired acrodermatitis enteropathica is treated with oral elemental zinc supplementation at 1 to 2 mg/kg daily.¹² Diarrhea typically resolves within 24 hours, but skin lesions heal in 1 to 2 weeks or longer. Although there is no consensus on when to discontinue zinc replacement therapy, therapy generally is not lifelong. Once the patient is zinc replete and the inciting factor has resolved, patients can discontinue supplementation without risk for recurrence.

Trace elements had not been added to our patient’s total parenteral nutrition prior to admission. Basic nutrition laboratory results and zinc levels returned markedly low: 14 μg/dL (reference range, 60–120 μg/dL). Alkaline phosphatase, a zinc-dependent protein, also was low at 12 U/L (reference range, 40–150 U/L). We added trace elements and vitamins and began empiric zinc replacement with 440 mg oral zinc sulfate daily (100 mg elemental zinc). Cephalexin was prescribed for impetiginized skin lesions. The patient noted skin improvement after 3 days on zinc replacement therapy.

Answer
The radiograph shows several abnormalities: There is a moderate to large right pleural effusion, as well as a parenchymal density within the right lower lobe. In addition, several of the ribs have a mottled appearance.

All of these findings are highly suspicious for primary as well as metastatic carcinoma. The patient was admitted to the hospital for further workup.

Answer
The radiograph shows several abnormalities: There is a moderate to large right pleural effusion, as well as a parenchymal density within the right lower lobe. In addition, several of the ribs have a mottled appearance.

All of these findings are highly suspicious for primary as well as metastatic carcinoma. The patient was admitted to the hospital for further workup.

Answer
The radiograph shows several abnormalities: There is a moderate to large right pleural effusion, as well as a parenchymal density within the right lower lobe. In addition, several of the ribs have a mottled appearance.

All of these findings are highly suspicious for primary as well as metastatic carcinoma. The patient was admitted to the hospital for further workup.

ANSWER
This ECG demonstrates normal sinus rhythm and diffuse ST elevations consistent with a diagnosis of pericarditis.

Although the QTc interval is long, it is due to the ST changes of pericarditis. Comparison with previous ECGs documented normal QTc intervals.

The patient’s pericarditis is most likely related to his recent viral illness. Following treatment with indomethacin, his symptoms resolved and his ECG normalized. Also, his abscess was managed by the surgical service and has since resolved.

ANSWER
This ECG demonstrates normal sinus rhythm and diffuse ST elevations consistent with a diagnosis of pericarditis.

Although the QTc interval is long, it is due to the ST changes of pericarditis. Comparison with previous ECGs documented normal QTc intervals.

The patient’s pericarditis is most likely related to his recent viral illness. Following treatment with indomethacin, his symptoms resolved and his ECG normalized. Also, his abscess was managed by the surgical service and has since resolved.

ANSWER
This ECG demonstrates normal sinus rhythm and diffuse ST elevations consistent with a diagnosis of pericarditis.

Although the QTc interval is long, it is due to the ST changes of pericarditis. Comparison with previous ECGs documented normal QTc intervals.

The patient’s pericarditis is most likely related to his recent viral illness. Following treatment with indomethacin, his symptoms resolved and his ECG normalized. Also, his abscess was managed by the surgical service and has since resolved.

ANSWER
The correct answer is pyogenic granuloma (choice “d”), further discussion of which follows. Bacillary angiomatosis (choice “a”) is a lesion caused by infection with a species of Bartonella—a distinctly unusual problem. While a retained foreign body (choice “b”), such as a splinter, could trigger a similar lesion, there was no relevant history to suggest this was the case here. The most concerning differential item, melanoma (choice “c”), can present as a glistening red nodule, especially in children, but this too would be quite unusual.

DISCUSSION
Pyogenic granuloma (PG) was the name originally given to these common lesions, which are neither pyogenic (pus producing) nor truly granulomatous (demonstrating a classic histologic pattern). Rather, they are the body’s frustrated attempt to lay down new blood supply in a healing but oft-traumatized lesion (eg, acne lesion, tag, nevus, or wart).

Other names for them include sclerosing hemangioma and lobular capillary hemangioma. Their appearance can vary from the classic look seen in this case to older lesions that tend to be drier and more warty.

PGs are far more common in children than in adults and greatly favor females over males. Pregnancy appears to trigger them, especially in the mouth, but they can appear on fingers, nipples, or even the scalp. Certain drugs, such as isotretinoin and certain chemotherapy agents, predispose to their formation.

PGs removed from children (by shave technique, followed by electrodesiccation and curettage) must be sent for pathologic examination to rule out nodular melanoma. That’s what was done in this case, with the pathology report confirming the expected vascular nature of the lesion.

ANSWER
The correct answer is pyogenic granuloma (choice “d”), further discussion of which follows. Bacillary angiomatosis (choice “a”) is a lesion caused by infection with a species of Bartonella—a distinctly unusual problem. While a retained foreign body (choice “b”), such as a splinter, could trigger a similar lesion, there was no relevant history to suggest this was the case here. The most concerning differential item, melanoma (choice “c”), can present as a glistening red nodule, especially in children, but this too would be quite unusual.

DISCUSSION
Pyogenic granuloma (PG) was the name originally given to these common lesions, which are neither pyogenic (pus producing) nor truly granulomatous (demonstrating a classic histologic pattern). Rather, they are the body’s frustrated attempt to lay down new blood supply in a healing but oft-traumatized lesion (eg, acne lesion, tag, nevus, or wart).

Other names for them include sclerosing hemangioma and lobular capillary hemangioma. Their appearance can vary from the classic look seen in this case to older lesions that tend to be drier and more warty.

PGs are far more common in children than in adults and greatly favor females over males. Pregnancy appears to trigger them, especially in the mouth, but they can appear on fingers, nipples, or even the scalp. Certain drugs, such as isotretinoin and certain chemotherapy agents, predispose to their formation.

PGs removed from children (by shave technique, followed by electrodesiccation and curettage) must be sent for pathologic examination to rule out nodular melanoma. That’s what was done in this case, with the pathology report confirming the expected vascular nature of the lesion.

ANSWER
The correct answer is pyogenic granuloma (choice “d”), further discussion of which follows. Bacillary angiomatosis (choice “a”) is a lesion caused by infection with a species of Bartonella—a distinctly unusual problem. While a retained foreign body (choice “b”), such as a splinter, could trigger a similar lesion, there was no relevant history to suggest this was the case here. The most concerning differential item, melanoma (choice “c”), can present as a glistening red nodule, especially in children, but this too would be quite unusual.

DISCUSSION
Pyogenic granuloma (PG) was the name originally given to these common lesions, which are neither pyogenic (pus producing) nor truly granulomatous (demonstrating a classic histologic pattern). Rather, they are the body’s frustrated attempt to lay down new blood supply in a healing but oft-traumatized lesion (eg, acne lesion, tag, nevus, or wart).

Other names for them include sclerosing hemangioma and lobular capillary hemangioma. Their appearance can vary from the classic look seen in this case to older lesions that tend to be drier and more warty.

PGs are far more common in children than in adults and greatly favor females over males. Pregnancy appears to trigger them, especially in the mouth, but they can appear on fingers, nipples, or even the scalp. Certain drugs, such as isotretinoin and certain chemotherapy agents, predispose to their formation.

PGs removed from children (by shave technique, followed by electrodesiccation and curettage) must be sent for pathologic examination to rule out nodular melanoma. That’s what was done in this case, with the pathology report confirming the expected vascular nature of the lesion.

The Diagnosis: Cutaneous Larva Migrans

Three punch biopsies were obtained. Spongiotic dermatitis with eosinophils was seen. There was a single specimen of tissue that showed a possible intraepidermal larva with a tract in the epidermis. The differential diagnosis included allergic contact dermatitis and arthropod bite eruption, among others, but clinical correlation made cutaneous larva migrans (CLM) the likely diagnosis.

The patient was treated empirically with albendazole 400 mg once daily for 3 days. In addition, he was prescribed triamcinolone for symptomatic relief and remained asymptomatic for 8 weeks at which time he presented again to the dermatology clinic with a similar rash in the same distribution. He was treated with a repeat course of albendazole and further educated on the etiology of the infection. The patient has not exhibited a recurrence after treatment of the second episode of CLM.

Cutaneous larva migrans is a dermatosis of the skin caused by the larvae of parasitic nematodes from the hookworm family, most commonly Ancylostoma caninum and Ancylostoma braziliense.^1,2 These hookworms thrive in warm moist climates and are most frequently found in tropical coastal regions. They normally inhabit the intestines of animals such as dogs and cats and are transmitted to soil and sand via feces. Humans become accidental hosts through contact with the contaminated sand or soil³; however, the larvae are unable to penetrate deeper than the upper dermis of the skin in humans, subsequently limiting the infection. Because humans are accidental hosts, the larvae are unable to complete their life cycle and larval death occurs within weeks to months after the initial infection³; thus treatment may be unnecessary unless complications arise.

Cutaneous larva migrans is most commonly observed in travelers or inhabitants of tropical coastal regions but can occur anywhere in the world.¹ Clinically, CLM presents as an enlarging, intensely pruritic, erythematous linear or serpiginous tract,³ most commonly on the hands, feet, abdomen, and buttocks.¹ Complications may include allergic reactions, secondary bacterial infections, and hookworm folliculitis.⁴ Although rare, migration to the intestinal tract⁵ and/or hematological spread with Löffler syndrome has been described.⁶ Although this dermatological disease has been well described in the medical literature, it is not well recognized by Western physicians and is consequently either not diagnosed or misdiagnosed, leading to delays in treatment.⁴ Although the infection is usually self-limiting without treatment, the risk for prolonged active disease may occur, with 1 reported case lasting up to 18 months.^4,5 The first indicator of CLM is intense pruritus localized to the site of infection.⁴ As the larvae migrate or creep, they create a lesion that may appear edematous with vesiculobullous lesions that are either serpiginous or linear.⁴ The differential diagnosis may include fungal infection, bacterial infection, and atypical herpes simplex infections; however, the key finding in CLM is the presence of undulating tracts localized to the borders of the lesion.² Patients may report experiencing a stinging sensation prior to the formation of the erythematous scaly papule,⁵ which is attributed to the initial penetration of the larva into the skin. This development, accompanied with a history of travel to tropical or subtropical regions, should elicit CLM as a likely diagnosis. Because hookworms are a type of helminth, they likely elicit an eosinophilic immune response and thus peripheral eosinophilia may be present.⁵

Effective treatment of CLM is accomplished with oral albendazole 400 mg once daily for 3 to 7 days.^2,7 Alternatively, oral ivermectin, topical thiabendazole, and cryosurgery can be used,² though albendazole currently is the preferred treatment of CLM.⁷

The Diagnosis: Cutaneous Larva Migrans

Three punch biopsies were obtained. Spongiotic dermatitis with eosinophils was seen. There was a single specimen of tissue that showed a possible intraepidermal larva with a tract in the epidermis. The differential diagnosis included allergic contact dermatitis and arthropod bite eruption, among others, but clinical correlation made cutaneous larva migrans (CLM) the likely diagnosis.

The patient was treated empirically with albendazole 400 mg once daily for 3 days. In addition, he was prescribed triamcinolone for symptomatic relief and remained asymptomatic for 8 weeks at which time he presented again to the dermatology clinic with a similar rash in the same distribution. He was treated with a repeat course of albendazole and further educated on the etiology of the infection. The patient has not exhibited a recurrence after treatment of the second episode of CLM.

Cutaneous larva migrans is a dermatosis of the skin caused by the larvae of parasitic nematodes from the hookworm family, most commonly Ancylostoma caninum and Ancylostoma braziliense.^1,2 These hookworms thrive in warm moist climates and are most frequently found in tropical coastal regions. They normally inhabit the intestines of animals such as dogs and cats and are transmitted to soil and sand via feces. Humans become accidental hosts through contact with the contaminated sand or soil³; however, the larvae are unable to penetrate deeper than the upper dermis of the skin in humans, subsequently limiting the infection. Because humans are accidental hosts, the larvae are unable to complete their life cycle and larval death occurs within weeks to months after the initial infection³; thus treatment may be unnecessary unless complications arise.

Cutaneous larva migrans is most commonly observed in travelers or inhabitants of tropical coastal regions but can occur anywhere in the world.¹ Clinically, CLM presents as an enlarging, intensely pruritic, erythematous linear or serpiginous tract,³ most commonly on the hands, feet, abdomen, and buttocks.¹ Complications may include allergic reactions, secondary bacterial infections, and hookworm folliculitis.⁴ Although rare, migration to the intestinal tract⁵ and/or hematological spread with Löffler syndrome has been described.⁶ Although this dermatological disease has been well described in the medical literature, it is not well recognized by Western physicians and is consequently either not diagnosed or misdiagnosed, leading to delays in treatment.⁴ Although the infection is usually self-limiting without treatment, the risk for prolonged active disease may occur, with 1 reported case lasting up to 18 months.^4,5 The first indicator of CLM is intense pruritus localized to the site of infection.⁴ As the larvae migrate or creep, they create a lesion that may appear edematous with vesiculobullous lesions that are either serpiginous or linear.⁴ The differential diagnosis may include fungal infection, bacterial infection, and atypical herpes simplex infections; however, the key finding in CLM is the presence of undulating tracts localized to the borders of the lesion.² Patients may report experiencing a stinging sensation prior to the formation of the erythematous scaly papule,⁵ which is attributed to the initial penetration of the larva into the skin. This development, accompanied with a history of travel to tropical or subtropical regions, should elicit CLM as a likely diagnosis. Because hookworms are a type of helminth, they likely elicit an eosinophilic immune response and thus peripheral eosinophilia may be present.⁵

Effective treatment of CLM is accomplished with oral albendazole 400 mg once daily for 3 to 7 days.^2,7 Alternatively, oral ivermectin, topical thiabendazole, and cryosurgery can be used,² though albendazole currently is the preferred treatment of CLM.⁷

The Diagnosis: Cutaneous Larva Migrans

Three punch biopsies were obtained. Spongiotic dermatitis with eosinophils was seen. There was a single specimen of tissue that showed a possible intraepidermal larva with a tract in the epidermis. The differential diagnosis included allergic contact dermatitis and arthropod bite eruption, among others, but clinical correlation made cutaneous larva migrans (CLM) the likely diagnosis.

The patient was treated empirically with albendazole 400 mg once daily for 3 days. In addition, he was prescribed triamcinolone for symptomatic relief and remained asymptomatic for 8 weeks at which time he presented again to the dermatology clinic with a similar rash in the same distribution. He was treated with a repeat course of albendazole and further educated on the etiology of the infection. The patient has not exhibited a recurrence after treatment of the second episode of CLM.

Cutaneous larva migrans is a dermatosis of the skin caused by the larvae of parasitic nematodes from the hookworm family, most commonly Ancylostoma caninum and Ancylostoma braziliense.^1,2 These hookworms thrive in warm moist climates and are most frequently found in tropical coastal regions. They normally inhabit the intestines of animals such as dogs and cats and are transmitted to soil and sand via feces. Humans become accidental hosts through contact with the contaminated sand or soil³; however, the larvae are unable to penetrate deeper than the upper dermis of the skin in humans, subsequently limiting the infection. Because humans are accidental hosts, the larvae are unable to complete their life cycle and larval death occurs within weeks to months after the initial infection³; thus treatment may be unnecessary unless complications arise.

Cutaneous larva migrans is most commonly observed in travelers or inhabitants of tropical coastal regions but can occur anywhere in the world.¹ Clinically, CLM presents as an enlarging, intensely pruritic, erythematous linear or serpiginous tract,³ most commonly on the hands, feet, abdomen, and buttocks.¹ Complications may include allergic reactions, secondary bacterial infections, and hookworm folliculitis.⁴ Although rare, migration to the intestinal tract⁵ and/or hematological spread with Löffler syndrome has been described.⁶ Although this dermatological disease has been well described in the medical literature, it is not well recognized by Western physicians and is consequently either not diagnosed or misdiagnosed, leading to delays in treatment.⁴ Although the infection is usually self-limiting without treatment, the risk for prolonged active disease may occur, with 1 reported case lasting up to 18 months.^4,5 The first indicator of CLM is intense pruritus localized to the site of infection.⁴ As the larvae migrate or creep, they create a lesion that may appear edematous with vesiculobullous lesions that are either serpiginous or linear.⁴ The differential diagnosis may include fungal infection, bacterial infection, and atypical herpes simplex infections; however, the key finding in CLM is the presence of undulating tracts localized to the borders of the lesion.² Patients may report experiencing a stinging sensation prior to the formation of the erythematous scaly papule,⁵ which is attributed to the initial penetration of the larva into the skin. This development, accompanied with a history of travel to tropical or subtropical regions, should elicit CLM as a likely diagnosis. Because hookworms are a type of helminth, they likely elicit an eosinophilic immune response and thus peripheral eosinophilia may be present.⁵

Effective treatment of CLM is accomplished with oral albendazole 400 mg once daily for 3 to 7 days.^2,7 Alternatively, oral ivermectin, topical thiabendazole, and cryosurgery can be used,² though albendazole currently is the preferred treatment of CLM.⁷

The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

The Diagnosis: Bullous Henoch-Schönlein Purpura

Laboratory tests in this patient showed no abnormalities for complete blood cell count, immunoglobulins, anti–double-stranded DNA, antinuclear antibody, p–antineutrophil cytoplasmic antibodies, lupus anticoagulant, Sjögren antibodies, liver enzymes, and erythrocyte sedimentation rate. Urinalysis was normal. Punch biopsies were obtained and a histologic examination showed an intense inflammatory infiltrate of neutrophils around blood vessels within the dermis (Figure). These blood vessels showed swollen endothelium and narrowing of the vessel lumina with leukocytoclasia. Direct immunofluorescence revealed granular IgA, C3, fibrin, and weak IgM deposits in blood vessels in the papillary dermis consistent with Henoch-Schönlein purpura (HSP).

Henoch-Schönlein purpura is the most common vasculitis in children.^1-6 However, its bullous variant is rare, with few pediatric cases reported. Bullous HSP affects arterioles through an IgA-mediated pathway.^1-6 It is believed that the bullae are formed secondary to neutrophilic release of matrix metalloproteinase 9 (MMP-9), which degrades extracellular collagen.² Additionally, bullous fluid from HSP has been noted to have markedly elevated levels of soluble CD23, a form of the CD23 B-cell surface receptor used in antibody feedback regulation and B-cell recruitment, which also has been found to be elevated in the fluid of bullous pemphigoid, suggesting a similar pathogenesis of exaggerated humoral immunity.³

The most common sign of HSP is palpable purpura; however, other cutaneous findings can be present including targetoid plaques, macules, papules, petechiae, and bullae that may become hemorrhagic, ulcerated, necrotic, or scarred.^1-6 Bullae appear in the most dependent parts of the body, such as the feet and lower legs. Hydrostatic pressure may play a role in the pathogenesis of this phenomenon.¹ When other classic signs of HSP are absent, the presence of bullae clouds the diagnosis and creates controversy regarding treatment, as there is a dearth of literature on proper therapy for severe cutaneous manifestations of HSP.⁶

Our patient was treated with morphine for pain management along with topical mupirocin and nonadherent dressings for wound care. She also received pulse intravenous methylprednisolone 2 mg/kg daily for 3 days and then was transitioned to oral prednisone 1 mg/kg daily, which was tapered over 3 weeks after discharge. This regimen resulted in resolution of symptoms with rapid regression of bullae and subsequent postinflammatory hyperpigmentation. Prior reports have noted that the presence of bullae does not alter the prognosis or predict probability of renal involvement of this self-limited disease, leading to controversy in determining if treatment offers more favorable outcomes.^1,3 One study suggested that steroids only improve symptoms, arthralgia, and abdominal pain, but they do not aid in the resolution of cutaneous lesions or prevent the progression of renal disease.³ Contrarily, others have suggested that the presence of bullae and renal disease is an indication to start treatment.⁶ This claim is based on the mechanistic finding that immunosuppression with corticosteroids decreases inflammation by inhibiting activator protein 1, a transcription factor for MMP-9, thereby reducing MMP-9 activity and the formation of bullae.⁴ Clinical anecdotes, including our own, that demonstrate dramatic improvement of hemorrhagic bullae with the administration of corticosteroids substantiate this mechanism. Through the inhibition of neutrophil interactions and IgA production, other anti-inflammatory and immunosuppressive medications such as colchicine, dapsone, and azathioprine also have been reported to aid in resolution of the cutaneous lesions.^1,5,6 Although there is a clear drawback to the lack of controlled trials and prospective studies regarding the treatment of bullous HSP, it is nearly impossible to expect such studies to be carried out given the rare and unpredictable nature of the disease. For now, claims derived from case series and case reports guide our understanding of treatment efficacy.

Acknowledgment—Quiz photograph courtesy of Steve Taylor, BS, Phoenix, Arizona.

Answer
The radiograph shows a compression deformity of the C6 vertebral body. In addition, there is a displaced fracture fragment along the anterior superior endplate. Alignment is adequate, with no evidence of subluxation. The disc space of C6-7 also appears slightly distracted, suggesting possible acute injury.

Given the clinical and radiographic presentation, this patient warranted further workup. He was admitted for CT and MRI of the cervical spine, which demonstrated disc herniation at both the C5-6 and C6-7 levels, as well as interspinous ligament injury.

The patient subsequently underwent a two-level anterior cervical disc­ectomy and fusion. His symptoms resolved, and he was discharged home the next day.

Answer
The radiograph shows a compression deformity of the C6 vertebral body. In addition, there is a displaced fracture fragment along the anterior superior endplate. Alignment is adequate, with no evidence of subluxation. The disc space of C6-7 also appears slightly distracted, suggesting possible acute injury.

Given the clinical and radiographic presentation, this patient warranted further workup. He was admitted for CT and MRI of the cervical spine, which demonstrated disc herniation at both the C5-6 and C6-7 levels, as well as interspinous ligament injury.

The patient subsequently underwent a two-level anterior cervical disc­ectomy and fusion. His symptoms resolved, and he was discharged home the next day.

Answer
The radiograph shows a compression deformity of the C6 vertebral body. In addition, there is a displaced fracture fragment along the anterior superior endplate. Alignment is adequate, with no evidence of subluxation. The disc space of C6-7 also appears slightly distracted, suggesting possible acute injury.

Given the clinical and radiographic presentation, this patient warranted further workup. He was admitted for CT and MRI of the cervical spine, which demonstrated disc herniation at both the C5-6 and C6-7 levels, as well as interspinous ligament injury.

The patient subsequently underwent a two-level anterior cervical disc­ectomy and fusion. His symptoms resolved, and he was discharged home the next day.

ANSWER
The correct answer is normal sinus rhythm, acute anterior myocardial infarction, and inferolateral injury.

A P wave for every QRS and a QRS for every P wave at a rate between 60 and 100 beats/min are indicative of normal sinus rhythm.

Acute anterior myocardial infarction is evidenced by the significant Q waves and ST elevations in leads I and V₂ to V₄ and inferolateral injury by ST elevations in limb leads II, III, and aVF and precordial leads V₅ and V₆.

Subsequent cardiac catheterization revealed an occlusion of the proximal left anterior descending coronary artery, as well as significant lesions in the posterior descending artery and a marginal branch of the circumflex coronary artery.

ANSWER
The correct answer is normal sinus rhythm, acute anterior myocardial infarction, and inferolateral injury.

A P wave for every QRS and a QRS for every P wave at a rate between 60 and 100 beats/min are indicative of normal sinus rhythm.

Acute anterior myocardial infarction is evidenced by the significant Q waves and ST elevations in leads I and V₂ to V₄ and inferolateral injury by ST elevations in limb leads II, III, and aVF and precordial leads V₅ and V₆.

Subsequent cardiac catheterization revealed an occlusion of the proximal left anterior descending coronary artery, as well as significant lesions in the posterior descending artery and a marginal branch of the circumflex coronary artery.

ANSWER
The correct answer is normal sinus rhythm, acute anterior myocardial infarction, and inferolateral injury.

A P wave for every QRS and a QRS for every P wave at a rate between 60 and 100 beats/min are indicative of normal sinus rhythm.

Acute anterior myocardial infarction is evidenced by the significant Q waves and ST elevations in leads I and V₂ to V₄ and inferolateral injury by ST elevations in limb leads II, III, and aVF and precordial leads V₅ and V₆.

Subsequent cardiac catheterization revealed an occlusion of the proximal left anterior descending coronary artery, as well as significant lesions in the posterior descending artery and a marginal branch of the circumflex coronary artery.