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Challenging the schemes: acantholytic (Darier's disease‐like) Kyrle's disease

To the Editor, The histopathologic differentiation of acantholytic dermatoses is often challenging,1 not only because they are basically similar each to the other, but also because they can even share the very same histopathologic features (e.g. Darier-like Grover’s disease,2 warty dyskeratoma-like comedonal Darier’s disease (DD)3). Much less commonly, non-acantholytic dermatoses can show acantholytic changes.4 We herein present a case of Kyle’s disease (KD) with acantholytic DD-like histopathologic features. Such a previously unreported case further expands the differential diagnosis of acantholytic dermatoses and underlines the need of a careful clinicopathologic correlation in this field of dermatopathology. A 58-year-old man was seen for a long-lasting widespread skin eruption. The patient had noticed the first papules on his legs during the childhood; the lesions had become larger, more widespread, and slightly pruritic over decades; they had never undergone spontaneous regression or improvement. There was no history of similar skin changes in other members of the family; the patient did not assume any drugs, with the exception of antihistamines in order to reduce the itch. On physical examination (Fig. 1), the skin eruption involved the lower limbs and, to a lesser extent, the upper limbs, the lower abdomen and the buttocks. The lesions were discrete, red-brown, dome-shaped papules and nodules measuring 0.3–1.5 cm, with a central keratin plug. Coalescence of some of these keratotic papules and nodules had given rise to verrucous plaques with a pseudoepitheliomatous clinical appearance. Neither the seborrheic areas of the trunk nor the mucous membranes was involved, no sign of nail dystrophy was found, physical examination was otherwise unremarkable and neurological examination was negative as well. Pertinent laboratory data, including liver and renal function tests, serum sugar, carotene, urea and creatinine were normal. Histologic examination of biopsy specimens taken in two different instances from the leg and from the abdomen showed a focal and irregular hyperplasia of the epidermis with an invagination of the infundibular epithelium (Fig. 2, top left); the latter was atrophic and superimposed by keratotic plug (Fig. 2, top right). Interestingly, the bottom of the plug disclosed acantholysis mostly localized in the upper malpighian layer and accompanied by dyskeratosis (Fig. 2, bottom left). The latter was strikingly akin to DD, with evidence of ‘corps ronds’ (cells with a perinuclear halo and a peripheral basophilic shell) and ‘grains’ (cells with pyknotic nuclei and homogeneous hypereosinophilic/basophilic cytoplasms) (Fig. 2, bottom right). In the dermis there was only a mild inflammatory infiltrate. Collagen (Van Gieson) and elastic (Weigert) tissue stains failed to show any abnormal architecture of the dermis. Because of the acantholytic features unexpectedly found on histopathology, molecular search for DD-associated mutations were carried out. The ATP2A2 (12q23-24.1) gene was amplified by means of polymerase chain reaction (PCR) from high molecular weight genomic DNA isolated from lymphocytes of the patient (sequence obtained from Sakuntabhai et al.5). However, denaturating high performance liquid chromatography (DHPLC) on PCR-amplified products6 – performed as previously described – failed to show any ATP2A2 gene mutation. Therefore, mainly on the basis of the clinical picture, a final diagnosis of KD was made. First described in 1916 as ‘hyperkeratosis follicularis et parafollicularis in cutem penetrans’,7 KD has often been a matter of clinicopathologic controversy. In 1968 Constantine and Carter8 summarized the diagnostic criteria of the disease, but the previously published cases they confirmed as KD were subsequently considered as examples of perforating folliculitis.9 The disease has been repeatedly reported in association with diabetes and/or with renal failure. Both conditions may be characterized by pruritus and the latter could even be responsible for keratotic lesions with the picking/scratching of the skin.