Case of the Month

A man (who was just released from prison) with a terrible rash told me: "my skin is so itchy it is driving me crazy, driving me totally out of my mind. The rash started 11 months ago when I was incarcerated. I have been treated with a lotion that I put all over my body and kept it on overnight. I did this 1 week apart for 3 separate weeks. They told me they were treating some type of mite or body lice infestation called scabies. I also took 3 separate courses of some pills named ivermectin. No change. Many of the itchy bumps start out like little tiny water blisters, especially on my arms, but they itch so much I scratch the tops off, and mostly I have scabs everywhere. The rash is now all over, but it started out on my forearms, butt, and scalp. Nothing is working, and it is getting worse, and I am doing everything I can to keep my sanity. I feel like I am in a living hell and it keeps getting worse."
On examination, there were no vibex between fingers or on the ventral wrists. No nodules in the axilla or glans of the penis. No extensive scaling. Only little vesicles and crusts from vesicles that had been scratched, especially on the dorsal forearms, buttocks, and head. He told me that he had no health insurance and said he did not have any additional money to pay for medications or tests. I used a grant from the Crutchfield Foundation to pay for his dermatopathology.

H &E
The epidermis shows mild acanthosis with exocytosis of occasional neutrophils. A subepidermal vesicle is present which contains numerous neutrophils, and clusters of neutrophils are also seen within dermal papillae. A mild to moderately intense mainly perivascular inflammatory infiltrate is present in the superficial and deep dermis, consisting of numerous neutrophils with some lymphocytes, eosinophils, and histiocytes.

Direct Immunofluorescence
IgG: Negative
IgM: Negative
IgA: Granular basement membrane zone and papillary dermal deposition
C3: Granular basement membrane zone and papillary dermal deposition
Fibrinogen: Patchy staining of connective tissue fibers
Comment: These findings are consistent with the clinical impression of dermatitis herpetiformis.

What's Your Diagnosis?

Diagnosis: DERMATITIS HERPETIFORMIS

DEFINITION: An inflammatory process characterized by symmetrical distribution, especially on the skin of the scalp, overlying the scapulae and the sacrum, on the buttocks, and on the extensor surface of the extremities, of clusters of urticarial papules, papulovesicles, and vesicles that are so intensely pruritic that they soon are scratched away, leaving in the wake erosions, ulcers, hemorrhagic crusts, and eventually pigmented macules and scars.

ADJUNCTIVE DIAGNOSTIC TESTS Demonstration of deposits of IgA situated at the tips of dermal papillae in both perilesional and normal-appearing skin. In severe cases, a biopsy of the small intestine can be performed to identify celiac-like disease caused by sensitivity to gluten.

COURSE Dermatitis herpetiformis tends to appear in young adults, but it may develop in children and in the elderly, usually as urticarial papules and vesicles that are clustered in bilateral symmetrical fashion especially on the scalp, scapulae, extensor surface of arms and legs (in particular the region of the elbows and knees), sacrum, and buttocks. The lesions wax and wane, and in the absence of specific therapy, tend to come and go for a lifetime. Episodically, and exceptionally, the disease remits, not to reappear.

INTEGRATION: UNIFYING CONCEPT Dermatitis herpetiformis is a distinctive pathologic process that manifests itself as urticarial papules and vesicles; these lesions have a predilection for specific anatomic sites. Papules are made up mostly of neutrophils in edematous dermal papillae and in subepidermal clefts, and subepidermal vesicles also contain neutrophils. Neutrophils are joined by eosinophils within two or three days after a lesion first appears. The disease is thought to be autoimmune in nature, granular deposits of IgA alone or in combination with C3 being present at tips of der-mal papillae. Although the cause and mechanism of dermatitis herpetiformis are not known, it is thought currently that deposits of IgA in the papillary dermis are related to hypersensitivity to gluten. Ingestion of gluten is believed to initiate formation of IgA antibodies in the gastrointestinal tract, circulation of those antibodies, attachment of them to cutaneous structures, activation of complement, chemotaxis of neutrophils, and development of subepidermal blisters. The process is believed to be a consequence of the effects of products released by neutrophils on the attachment of the epidermis to the dermis. A gluten-sensitive enteropathy resembling celiac disease is commonly associated with dermatitis herpetiformis. The histopathologic findings in linear IgA dermatosis are identical to those in dermatitis herpetiformis, but the clinical aspects and immunologic attributes of those diseases are different from one another. THERAPY Dapsone is effective, presumably by suppressing neutrophils. An option therapeutically is sulfapyridine. A diet free of gluten, although extraordinarily difficult to achieve, may improve the skin disease.

In this particular case, I initiated oral prednisone for immediate relief, which helped a great deal, while I ordered a G6PD enzyme check (to make sure he could tolerate Dapsone). His G6PD was and I started him on dapsone, 100mg a day for the first week, then 100mg BID thereafter. He reported after 2 weeks that he was completely clear and happy. I monitored the dapsone as follows: CBC qwk x4, qmo x6, then q6mo thereafter; LFTs at baseline, then periodically.

Reference: A CLINICAL ATLAS OF 101 COMMON SKIN DISEASES With Histopathologic Correlation A. BERNARD ACKERMAN, HELMET KERL, JORGE SANCHEZ, YING GUO, ANGELIKA HOFER, PAUL KELLY, TETSU KIMURA, GIOVANNI BORRONI,CHARLES CRUTCHFIELD, VOLKER STEINKRAUS, WOLFGANG WEYERS

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