Leukocytoclastic Vasculitis as the Presenting Feature of Dermatitis Herpetiformis FREE

Dermatitis herpetiformis (DH) is a well-known autoimmune disease typically characterized by pruritic vesicles located on the extensor surfaces. Classic disease consists of neutrophils within the dermal papillae. Additional histopathologic findings include fibrin deposition and edema within the dermal papillae. Subepidermal vesicles also may be present. Direct immunofluorescence demonstrates granular deposition of IgA in the dermal papillae. Typically, patients with DH demonstrate elevated levels of serum IgA antitissue transglutaminase or IgA endomysial antibodies. Also, they may have gastrointestinal symptoms related to the disease and may show a flattened villous architecture on small bowel biopsy specimens. Treatment typically consists of a gluten-free diet or dapsone.

A 58-year-old man had a 9-month history of tender petechiae on the hands, feet, ankle, thigh, and knee (Figure 1). He also reported a history of psoriasis. The results of workup for systemic vasculitis, including urinalysis; erythrocyte sedimentation rate; C-reactive protein; complete blood cell count; basic metabolic panel; liver function tests; anti-DNA tests; total hemolytic complement; complement profile; partial thromboplastin time; prothrombin time; rheumatoid factor; and antineutrophil cytoplasmic, ribonucleoprotein, Smith, Ro, and La antibodies testing, were negative. The antinuclear antibody test result was positive to a dilution of 1:160. The patient subsequently developed mildly pruritic, erythematous macules, pustules, and crusted papules ranging from 2 to 6 mm in diameter on the bilateral aspect of the knees, elbows, forearms, scalp, and neck (Figure 2). The patient's review of systems revealed episodes of loose stool, which had occurred several times a week since adolescence.

The initial biopsy specimen of the finger demonstrated findings consistent with leukocytoclastic vasculitis (LCV), including perivascular neutrophils, extravasated red blood cells, and fibrin deposition in the vessels (Figure 3). Classic features of DH were not seen. Eleven months later, a biopsy specimen from the right arm demonstrated spongiosis with a mixed inflammatory infiltrate predominantly in a perivascular distribution. Only rare neutrophils were seen in the papillary dermis. The biopsy specimens from the left arm and the right leg demonstrated prominent LCV in the superficial and middle dermis along with features of DH, including neutrophils and edema in the dermal papillae and the formation of subepidermal vesicles (Figure 4A-C). Of interest, acute folliculitis also was seen (Figure 4D). Direct immunofluorescence revealed granular deposition of IgA in the dermal papillae and the dermoepidermal junction (Figure 5). Deposition of IgA was not seen in the vessel walls. Intermittent granular deposits of C3 and fibrin also were noted at the dermoepidermal junction.

Further workup revealed an elevated serum IgA antitissue transglutaminase level of 57 (moderate to strong positive >30) units. A jejunal biopsy specimen demonstrated mild chronic inflammation with preservation of the normal villous architecture. The biopsy had been performed after the patient was started on a gluten-free diet. In addition, the lack of villous blunting changes may have been due to sampling error. The patient reports partial adherence to the diet with marked improvement in his skin disease and a decrease in the frequency of loose stools. He was not treated with dapsone because he was responding to a gluten-free diet.

Previously reported cases of petechiae in DH have been restricted to the palmar and, more rarely, to the plantar surfaces.^1- 3 In the series by Karpati et al² of 47 children with DH, 30 were found to have palmar lesions and 3 to have plantar lesions. These lesions were described clinically as red-brown macules and blisters. Although distribution on the acral surfaces is a well-known clinical pattern in children, this presentation in adults only rarely has been reported.^1,4 Our patient's petechiae involved a broader clinical distribution than the cases previously described, including the ankle, thigh, and knee.

In the English-language literature, most of the petechiae found in the setting of DH were not biopsied. Of the lesions with histopathologic findings reported, most describe classic features of DH along with extravasated red blood cells.^4- 5 Petechial lesions of DH also may show a perivascular mixed inflammatory cell infiltrate,³ as also demonstrated in our patient. However, his case is unusual in that the initial presentation was of LCV. In addition, our patient has acute folliculitis within a petechial lesion of DH. This, however, may be a separate process because folliculitis is a relatively common disease.

One case of DH has been reported with associated cutaneous vasculitis, but this was described in the clinical setting of erythema elevatum diutinium.⁶ Other authors⁷ have drawn attention to the similarity seen between upper dermal edema and the potential for vesicle formation in LCV and DH. Of importance, our case documents the presence of LCV in petechiae caused by DH. Although reports have been published^8- 9 of DH occurring within petechial lesions, it is unusual for LCV to present as petechiae, which further supports the theory that DH and LCV are part of the same process in this case. Perhaps the LCV is secondary to the recruitment of neutrophils in DH as it is in other diseases, such as Sweet syndrome and granuloma faciale.

Jones and Bhogal⁷ reported a case of LCV with clinical and histopathologic features of DH, including direct immunofluorescence of perilesional skin with granular IgA in the upper dermis. They described the similarity of superficial dermal edema and the potential for vesicle formation in LCV and DH but concluded that their case constituted LCV and not DH because no immunofluorescent IgA was seen in the dermoepidermal junction in uninvolved skin. We hypothesize that this case actually may represent DH. Other authors have found that healthy skin less frequently tests positive for IgA¹⁰; therefore, some advise the use of a perilesional rather than a normal or involved skin biopsy for direct immunofluorescence as the criterion standard for diagnosing DH.^10- 11 Although we did not perform direct immunofluorescence of uninvolved skin, the response to a gluten-free diet gives further evidence that our patient has DH. We believe that the case by Jones and Bhogal, as well as that presented herein, are actually 2 unique cases of LCV found in the setting of DH. Leukocytoclastic vasculitis may be prominent in DH and can be found as the initial histologic manifestation of the disease.