A Case of Multiple Necrotic Dyskeratotic Cells within the Upper Epidermis and Horny Layer Revealing Persistent Papules and Plaques of Adult-Onset Still’s Disease

It is difficult to differentiate asymptomatic papules and plaques that widely persist on the trunk and extremities. Particularly, when dyskeratotic cells are observed in biopsy, lupus erythematosus (LE), dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD) should be considered1, 2. Dyskeratotic cells only in the upper epidermis and horny layer are not well known, but it is a distinctive histopathological reactive pattern of atypical type of rash associated with adult-onset Still’s disease (AOSD)3. Herein, we present a case with characteristic necrotic dyskeratotic cells in the upper epidermis and horny layer without any AOSD symptoms lasting for five years.

A 75-year-old patient presented with widespread, persistent skin lesions on the trunk and extremities. The lesion occurred five years ago and accompanied by intermittent mild pruritus for the onset until now. Erythematous to brownish edematous patches and plaques were observed in the bilateral extensor surface of the arms, neck, upper chest, and lower extremities, without oral, ocular, or genital lesions (Fig. 1). There was no underlying disease. To exclude connective tissue diseases, such as LE, DM, or malignancies, such as mycosis fungoides, histopathologic examination was performed for three lesions, including the upper and lower trunk, and lower leg. The incisional biopsy of erythematous plaques on the patient’s upper trunk revealed multiple necrotic dyskeratotic cells in the upper epidermal and horny layer, along with mild superficial perivascular lymphocytic infiltration (Fig. 2A, B). Immunohistochemical staining revealed cytokeratin-positive dyskeratotic cells and increased mucin deposition in the upper dermis (Fig. 2C, D), but these were negative for herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus, and pan-human papillomavirus stain. The same findings were observed in the other two specimens. Laboratory examinations revealed no significant findings, with no leukocytosis or neutrophilia. His ferritin level (27 ng/ml; reference range, 16~400 ng/ml) was also normal, and his antinuclear antibody and rheumatoid factor were negative. The patient was referred to the Department of Rheumatology to exclude other connective tissue diseases or underlying malignancies. There were no specific findings, and chest computed tomography revealed no abnormalities. Systemic steroid and topical calcipotriene and betamethasone combination were used to improve the skin symptoms; however, the response was limited. There was no evidence of AOSD based on the systemic symptoms or laboratory results of this patient. Based on a close history taking, there was a previous hospitalization for fever and arthritis that lasted for several days and disappeared five years ago, at which time a skin lesion developed and persisted. When checking the Yamaguchi criteria4, two of the major criteria were satisfied, but it was difficult to confirm clearly according to the criteria because the previous record for laboratory evaluation could not be confirmed. However, it could be estimated that an atypical type of rash remained after AOSD. After that, systemic methotrexate (MTX) (10 mg/week) was used, and the lesions exhibited a partial improvement, as the plaques were flattened after a month.

Fig. 1
Erythematous to brownish edematous patches and plaques involving the bilateral extensor surface of the arms (A), neck, upper chest (B), and lower extremities (C). Close-up view (D). We received the patient’s consent form about publishing all photographic materials.

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Fig. 2
Histopathologic examination shows dyskeratotic keratinocytes in the upper epidermal layer and horny layer, along with mild superficial perivascular lymphocytic infiltration (A: H&E, original magnification ×40; B: H&E, original magnification ×200). Immunohistochemical staining reveals cytokeratin-positive dyskeratotic cells (C: cytokeratin staining, original magnification ×100). Increased mucin deposition can be observed in the upper dermis (D: alcian blue staining; original magnification ×100).

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AOSD is a diagnosis of exclusion; it can be diagnosed after infection, malignancy, or other connective tissue diseases have been ruled out5. Its common rash is a transient, salmon-colored rash that occurs and disappears with fever5, 6. However, an atypical type of rash called “persistent dermal plaque” or “persistent pruritic eruptions” has also been reported; it occurs on the neck, back, and extensor surfaces, with papules and plaques that persist even after fever subsides, similar to our patient3, 7, 8, 9, 10. In this case, the lesions occurred with these atypical eruptions of AOSD favoring distribution. It can also be involved in the pathogenesis of some lesions, as it is observed in the exposed areas. In the previous reports of atypical eruptions, more than half of the cases revealed mucin deposition in the dermal layer, similar to this case. This might be a basis for supporting this result due to secondary degeneration after physical stimuli or Koebner’s phenomenon2, 10.

The lesion is also known to be gradually improved according to the use of systemic corticosteroids11. However, most of the literatures were focused on the prognostic aspect, and the skin lesions were deal with in only 6 out of 40 cases in the literature review10. There was one case each that showing improvement by MTX and anakinra (interleukin [IL]-1 receptor antagonist) because there was no response to steroids, but this also improved over several months medication with residual hyperpigmentation without mentioning the exact period12. Multiple cytokines are involved in the pathogenesis of AOSD. IL-18 combines with keratinocytes to induce apoptosis, and its treatment response was slower than AOSD without dyskeratotic cells3, 5, 10. Although the lesions were old, and the serum IL-18 level of this patient could not be measured, the lesions showed improvement after MTX administration. Since the IL-18 level could be lowered after MTX treatment13, As a result of this mechanism, it could be considered that the lesions of patient has also improved.

This atypical eruption should be differentiated from various dermatoses that present with widespread violaceous to dusky red papules and plaques with dyskeratotic cells histopathologically. The differential diagnoses include LE, DM, drug eruptions, and GVHD. The presence of dyskeratotic keratinocytes in the upper epidermis, in association with neutrophilic and lymphocytic infiltration in the upper dermis without epidermal atrophy, is a distinct histological feature of these eruptions2, 12. Dyskeratotic keratinocytes are distributed in the lower epidermis in LE and DM, and these are accompanied by epidermal atrophy and lymphocytic infiltration in the dermis and periadnexal infiltration. Drug eruption could be differentiated from eosinophil infiltration. Although direct immunofluorescence and muscle enzyme evaluation were not conducted, there were no history and histopathological findings that suggest GVHD.

Although the atypical eruptions of AOSD are not rare, there were no Korean reports and no reports about lesions that lasted for such a long time; therefore, we report this case to introduce these characteristics with findings that are not well known.