Bullous pemphigoid associated with cutaneous leukocytoclastic vasculitis

UK A 79‐year‐old man presented with palpable purpura and poorly defined erythematous plaques on his limbs ( Fig. 1). History, examination, and clinical investigations (which included a full blood count, urea, electrolyte, and liver function tests, negative antinuclear and DNA antibodies, antineutrophil cytoplasmic antibody (ANCA), and cold agglutinins) showed no systemic involvement or triggering factors. He had not lost weight and took no medication. A diagnosis of cutaneous vasculitis was made and the patient's eruption improved with bed rest. He returned 2 months later with widespread tense blisters ( Fig. 2) and an erythrocyte sedimentation rate (ESR) of 90. The blisters were symmetrically distributed and sited predominantly on the flexural aspects of the upper limbs and trunk. Additional investigations were performed, with negative blood cultures, chest X‐ray, sputum cytology, sigmoidoscopy, fecal occult bloods, mid‐stream urine, abdominal ultrasound, and echocardiogram. He responded well to oral corticosteroids, with a rapid reduction in ESR. Twelve months later his condition remains well controlled on 7.5 mg of prednisolone daily. 1Painful palpable purpura on the left thigh2Tense blisters on the patient's left arm 2 months later Histopathology of the skin from an area of palpable purpura on the upper aspect of the thigh showed an intense leukocytoclastic vasculitis ( Fig. 3). The upper portion of the dermis showed foci of fibrinoid necrosis of small vessels associated with vessel wall permeation by neutrophil polymorphs and mononuclear inflammatory cells. Surrounding the vessels and throughout the dermis there was conspicuous leukocytoclasia. No epidermal separation or blister formation were present, but eosinophils were noted to be abundant in the infiltrate. Skin biopsy from an erythematous plaque on the upper limb showed similar features, with prominent leukocytoclasia, endothelial swelling, and edema. Direct immunofluorescence of perilesional skin showed strong linear deposition of immunoglobulin G (IgG) at the dermo‐epidermal junction. 3Photomicrograph demonstrating fibrinoid capillary necrosis in the dermis due to leukocytoclastic vasculitis. Note the prominent eosinophils in the infiltrate (hematoxylin and eosin stain; original magnification, ×400) Histopathology from a subsequent bullous lesion demonstrated a subepidermal blister containing serum exudate, fibrin, and many eosinophils ( Fig. 4). In the underlying dermis there was a perivascular and diffuse mononuclear infiltrate with prominent eosinophils. No leukocytoclastic vasculitis was evident. The roof of the blister was composed of normal epidermis. The appearance was entirely consistent with bullous pemphigoid. 4Bullous pemphigoid. A subepidermal blister containing an exudate rich in eosinophils (hematoxylin and eosin stain; original magnification, ×400)Discussion Cutaneous bullous pemphigoid has a worldwide distribution and is the most common autoimmune blistering dermatosis. 1 It is characterized by a widespread eruption of tense bulla on normal or erythematous skin. Histologically, the finding of a subepidermal blister associated with an infiltrate of eosinophils in the blister and underlying skin is suggestive of the diagnosis. This is supported by the finding of linear immunoglobulin G (IgG) and/or C3 at the dermo‐epidermal junction, which occurs in the vast majority of patients. Up to 80% of patients show anti‐basement membrane antibodies in the serum. 2 Before blistering occurs, a variety of prodromal skin eruptions may be seen. 3 , 4 These may be erythematous, urticarial, or occasionally eczematous. Histologically, a prodromal biopsy may show only nonspecific dermal edema with a perivascular and interstitial mononuclear infiltrate with eosinophils. Eosinophilic spongiosis is also frequently seen. 5 Direct immunofluorescence may be positive on skin biopsies taken before the blisters are manifest. 3 , 4 Cutaneous leukocytoclastic vasculitis has many associations, including bacterial or viral infections, reactions to drugs or toxins, systemic lupus erythematosus (SLE), and various malignancies. 6 It results from immune complex deposition in vessels leading to complement activation. Histologic examination shows fibrinoid necrosis of capillaries and post‐capillary venules with endothelial swelling. Vessel walls show infiltration by neutrophil polymorphs and mononuclear cells and there is surrounding leukocytoclasia. Classically, direct immunofluorescence shows patchy perivascular immunoglobulin and complement deposition in early lesions. 7 To the best of our knowledge, leukocytoclastic vasculitis has never been described in association with established or prodromal bullous pemphigoid. Indeed, an authoritative text of dermatopathology 8 states that leukocytoclasia or a vasculitis are never seen.