Leprosy

To the Editor: We read with great interest the very interesting article written by Rongioletti et al1 about the pitfalls in rendering a correct diagnosis of leprosy in a nonendemic area. As a practicing pathologist responsible for a Brazilian dermatopathology laboratory with a volume of more than 8000 skin biopsies per year, of which 180 were histopathologically confirmed cases of leprosy during the past year, I would like to state that even in one of the most leprosy endemic areas of the world,2 the diagnosis of leprosy could be, and very often is, challenging, especially in the paucibacillary forms. This is even further complicated when the lesions are small; the biopsies are not properly preserved and demonstrate crushing artifact and it is difficult to identify nerve bundles; when the clinical information is not accurate and/or the clinical/histopathological picture is not a “classical” one. We would like to report a challenging case, which highlights these points. In March of the current year, we examined a skin sample of a 29-year-old machine operator of a mining company in the northern part Brazil. The patient had a short history of febrile lymphadenopathy which hstopathologically was diagnosed as Kikuchi-Fujimoto disease. The patient was HIV negative. He was treated with oral corticosteroid and had recent withdrawn from azathioprine after an acute episode of tracheobronchitis (treated with azithromycin); which started, in February, with malaise, neutrophilia, and multiple papulo-erythematous slightly tender lesions throughout the extremities, trunk, and face, sometimes with small vesicles in their summits (Fig. 1). The initial clinical hypothesis was dermatitis associated with Kikuchi-Fujimoto disease as, a few months earlier the possibility of leprosy was discarded.FIGURE 1: Papuloerythematous lesions on the face, sometimes with small vesicles in their summits.Serial histopathological sections from a skin biopsy revealed intra and subepidermal vesicles associated to vacuolar alteration of the basal layer. There was prominent edema of the papillary dermis; and dense mixed inflammatory infiltrate of histiocytes, lymphocytes, and neutrophils involving the entire thickness of the dermis, the dermal hypodermic interface, and the subcutaneous tissue in a lobular pattern, contrasting with the typical appearance of erythema nodosum (Figs. 2, 3). Focally, there were foci of leukocytoclastic vasculitis and perineural, but not intraneural, inflammatory infiltrates on the deep reticular dermis (Figs. 4, 5). Numerous acid-fast lepra bacilli (Wade-Fite stain) were demonstrated with a fragmented and granular outline (Fig. 6). Of great importance for the correct diagnosis of the case was the open dialogue with the referring physician. The final diagnosis was leprosy reaction type 2 [erythema nodosum leprosum (ENL)], and the patient was treated with thalidomide, dapsone, rifampin, clofazimine, and prednisone. Nowadays, the patient is well and symptomless.FIGURE 2: Intra- and subepidermic vesiculation, substantial edema of the papillary dermis, and dense mixed inflammatory infiltrate compromising the entire thickness of the dermis and the subcutaneous tissue in a lobular panniculitis pattern (hematoxylin and eosin, ×40).FIGURE 3: Intra- and subepidermic vesiculation adjoined to vacuolar alteration of the basal keratinocytes; substantial edema of the papillary dermis; and dense mixed inflammatory infiltrate of histiocytes, lymphocytes, and neutrophils (hematoxylin and eosin, ×100).FIGURE 4: Perineural inflammatory infiltrate (hematoxylin and eosin, ×400).FIGURE 5: Leukocytoclastic vasculitis (hematoxylin and eosin, ×400).FIGURE 6: Acid-fast lepra bacilli (Wade–Fite stain) with a fragmented and granular outline (×400).A complication of multibacillary leprosy,3 ENL, is regarded as a type III hypersensitivity reaction in Coombs and Gell classification. ENL most often occurs during the course of treatment; however, there have been described cases in which ENL is the first expression of the disease.4 In the current case, the confounding factors were a history of the Kikuchi-Fujimoto disease, the usage of immunosuppressant therapy, and the vesicular presentation of the disease, which raise the possibility of Kikuchi–Fujimoto-associated dermatitis, bullous lupus erythematosus, polymorphic erythema, and polymorphic light eruption. Many patients with Kikuchi disease have no cutaneous findings; however, a skin rash has been reported in a few cases, at times, with vacuolar alteration of the basal epithelial layer, replicating what is seen in lupus erythematosus.5–7 The histopathological clues which helped us to establish the correct diagnosis, were the distribution of the inflammatory cells roughly parallel to the surface of the epidermis and the loose arrangement of the granulomas with discernible Virchow cells (macrophages with ample granular cytoplasm). We are not aware that anybody in Brazil utilizes the S100 protein as an auxiliary tool for the diagnosis of leprosy. To conclude, 2 words of caution: whenever there is a perineural inflammatory infiltration an acid-fast stain should be performed and most important use the telephone which is the dermatopathologist's best friend.