Review
Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy

Presented at the Medical Dermatology Society Meeting, Denver, CO, March 20, 2014.
https://doi.org/10.1016/j.jaad.2015.04.063Get rights and content

Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

Introduction

Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is classically characterized by intermittent spiking fevers, an evanescent eruption, and arthralgias or arthritis with laboratory findings of leukocytosis and hyperferritinemia in the setting of a negative antinuclear antibody (ANA) test.1, 2, 3 Laboratory markers are suggestive of AOSD, but clinicians often rely on the typical evanescent eruption of light pink papules to make the diagnosis. Several classification criteria have been proposed; the Yamaguchi criteria are the most commonly used.2, 4, 5, 6 The major criteria are high fever for >1 week, arthralgias for >2 weeks, leukocytosis (>10,000/mm3 with >80% polymorphonuclear leukocytes), and the typical skin eruption. Minor criteria include sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction (ie, transaminitis), and the absence of rheumatoid factor and ANA.2 Recently, small studies and case reports have described an atypical, persistent skin rash consisting of pruritic papules and plaques with various configurations with distinct histopathology in patients with active AOSD.7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 This atypical rash often presents in addition to the typical rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In addition to these reports of atypical cutaneous presentations, emerging literature highlights an increasing recognition of malignancy in association with Still disease, sometimes occurring years later. Additional laboratory workup and close clinical follow-up may be warranted once a diagnosis of AOSD is made. We review the literature on AOSD to highlight these emerging concepts in the recognition and management of patients with Still disease.

Section snippets

Literature review of clinical presentations in patients with Still disease with atypical skin rashes

We searched PubMed-MEDLINE for English and non–English language articles available between January 1, 1980 and October 15, 2013 for case reports or population-based studies of atypical, persistent skin eruptions in adult patients with AOSD. Searching with the MeSH term “adult onset Still disease” and the terms “skin rash” or “persistent,” we retrieved 109 articles. Inclusion criteria included case reports or series reporting specific characteristics of an atypical skin eruption in adults

Adult-onset Still disease in association with malignancy

AOSD may present with nonspecific symptoms (ie, fever, lymphadenopathy, and hyperferritinemia), and therefore malignancy is an important diagnosis to exclude in the initial evaluation of a patient suspected to have this disease. However, recent literature has highlighted the emerging concept that these malignancies may not be found until months or years later. Traditionally, lymphoma has been known to mimic symptoms of Still disease, but leukemias and solid tumors have also been found to occur

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    Funding sources: None.

    Conflicts of interest: None declared.

    Drs Sun and Brezinski contributed equally to this work.

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