Adult-Onset Still Disease: Persistent Pruritic Papular Rash With Unique Histopathologic Findings
Adult-onset Still disease (AOSD) is a systemic inflammatory condition that manifests clinically through spiking fevers, arthralgia, evanescent skin rash, and lymphadenopathy. The most commonly used criteria for diagnosing AOSD are the Yamaguchi criteria. The major criteria include high fever for more than 1 week, arthralgia for more than 2 weeks, leukocytosis, and an evanescent skin rash. The minor criteria include sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and negative rheumatoid factor and antinuclear antibodies. Classically, the skin rash is described as an evanescent, salmon-colored erythema involving the extremities. Nevertheless, unusual cutaneous eruptions of AOSD have included persistent pruritic papules and plaques. Importantly, this atypical rash demonstrates specific histologic findings that are not found on routine histopathology for a typical evanescent rash. We describe 2 patients with this atypical cutaneous eruption along with the unique histopathologic findings of AOSD.
Practice Points
- Serologic testing and skin biopsy are necessary in the timely and appropriate diagnosis of adult-onset Still disease (AOSD).
- In patients with a persistent pruritic papular rash, consider AOSD if there is a supporting history.
- Skin biopsy is diagnostic of AOSD with the unique histopathologic findings of dyskeratotic keratinocytes in the cornified layers as well as in the epidermis and a sparse neutrophilic and/or lymphocytic infiltrate in the papillary dermis without vasculitis.
Comment
Adult-onset Still disease is a systemic inflammatory condition that clinically manifests as spiking fevers, arthralgia, salmon-pink evanescent erythema, and lymphadenopathy.2 The condition also can cause liver dysfunction, splenomegaly, pericarditis, pleuritis, renal dysfunction, and a reactive hemophagocytic syndrome.1 Furthermore, one review of the literature described an association with delayed-onset malignancy.4 Early diagnosis is important yet challenging, as AOSD is a diagnosis of exclusion. The Yamaguchi criteria are the most widely used method of diagnosis and demonstrate more than 90% sensitivity.In addition to the Yamaguchi criteria, marked hyperferritinemia is characteristic of AOSD and can act as an indicator of disease activity.5 Interestingly, both of our patients had elevated ferritin levels, with patient 2 showing marked elevation (Table). In both patients, all major criteria were fulfilled, except the typical skin rash.
The skin rash in AOSD, classically consisting of an evanescent, salmon-pink erythema predominantly involving the extremities, has been observed in up to 87% of AOSD patients.5 The histology of the typical evanescent rash is nonspecific, characterized by a relatively sparse, perivascular, mixed inflammatory infiltrate. Notably, other skin manifestations may be found in patients with AOSD.1,2,5-16 Persistent pruritic papules and plaques are the most commonly reported nonclassical rash, presenting as erythematous, slightly scaly papules and plaques with a linear configuration typically on the trunk.2 Both of our patients presented with this atypical eruption. Importantly, the histopathology of this unique rash displays distinctive features, which can aid in early diagnosis. Findings include dyskeratotic keratinocytes in the cornified layers as well as in the epidermis, and a sparse neutrophilic and/or lymphocytic infiltrate in the papillary dermis without vasculitis. These findings were evident in both histopathologic studies of our patients (Figures 2 and 4). Although not present in our patients, dermal mucin deposition has been demonstrated in some reports.1,13,15
A 2015 review of the literature yielded 30 cases of AOSD with pruritic persistent papules and plaques.4 The study confirmed a linear, erythematous or brown rash on the back and neck in the majority of cases. Histologic findings were congruent with those reported in our 2 cases: necrotic keratinocytes in the upper epidermis with a neutrophilic infiltrate in the upper dermis without vasculitis. Most patients showed rapid resolution of the rash and symptoms with the use of prednisone, prednisolone, or intravenous pulsed methylprednisolone. Interestingly, a range of presentations were noted, including prurigo pigmentosalike urticarial papules; lichenoid papules; and dermatographismlike, dermatomyositislike, and lichen amyloidosis–like rashes.4 In our report, patient 2 presented with a rash in a dermat-omyositislike shawl distribution. It has been suggested that patients with dermatomyositislike rashes require more potent immunotherapy as compared to patients with other rash morphologies.4 The need for methotrexate in addition to a prednisone taper in the clinical course of patient 2 lends further support to this observation.
,Conclusion
A clinically and pathologically distinct form of cutaneous disease—AOSD with persistent pruritic papules and plaques—was observed in our 2 patients. These histopathologic findings facilitated timely diagnosis in both patients. A range of clinical morphologies may exist in AOSD, an awareness of which is paramount. Adult-onset Still disease should be included in the differential diagnosis of a dermatomyositislike presentation in a shawl distribution. Prompt diagnosis is essential to ensure adequate therapy.
