Adult-onset Still's disease (AOSD) is a systemic inflammatory disease with unknown etiology. It is classically characterized by a high spiking fever, evanescent rash, liver dysfunction, leukocytosis with neutrophilia, generalized lymphadenopathy, and splenomegaly. The typical skin rash of AOSD is evanescent, appearing and disappearing along with the rise and fall of the fever. However, recent reports have highlighted atypical rashes associated with AOSD, such as persistent pruritic plaques and papules. We herein report a case of AOSD with persistent pruritic papules on the chest in a 47-year-old woman, who was suspected of septicemia and lymphoma for more than 3 weeks before diagnosis confirmed.
A 47-year-old woman presented with a 3-week history of an intermittent high fever, throat pain, and pruritic papules on the chest in Affiliated Hospital of Xuzhou Medical University. Before hospitalization, she had been repeatedly treated with antibiotics and antipyretics with unsatisfactory curative effects at a local hospital. Her personal and family medical histories were unremarkable.
Physical examination revealed confluent erythematous papules with slight scales on the chest (Fig. 1). Her fauces had a congestive appearance, and her lymph nodes were palpable on both sides of the neck. Polyarthralgia was obvious in her left wrist and right knee. Abnormal laboratory examination findings were leukocytosis (17.5 × 109/L) with 91.0% neutrophils, an elevated C-reactive protein level (76.9 mg/L), an elevated erythrocyte sedimentation rate (78 mm/h), and a high ferritin level (1,688 ng/ml). Her aspartate aminotransferase and alanine aminotransferase levels were 118 and 57 U/L, respectively. An infectious workup and extensive rheumatologic panel were otherwise negative. A whole-body positron emission tomography-computed tomography study showed enlarged lymph nodes in the bilateral neck and axillary and inguinal areas without involvement of other organs. Histo-pathologic examination of the pruritic papules showed hyperkeratosis with patchy parakeratosis, multiple areas of dyskeratosis confined to the upper layers of the epidermis, mild acanthosis, subtle vacuolar interface alteration, and a sparse dermal mixed infiltrate consisting of lymphocytes admixed with neutrophils and eosinophils (Fig. 2).
The patient was therefore diagnosed with AOSD, and given intravenous methylprednisolone at a dosage of 60 mg daily and methotrexate at a dosage of 10 mg weekly. Her symptoms, including the fever and skin lesions, gradually improved and eventually disappeared.
Still's disease is divided into juvenile-onset Still's disease (JOSD) and AOSD. The former includes JOSD involving one or a few joints, JOSD involving multiple joints, enthesitis-related JOSD, and psoriasis-related JOSD. AOSD is a systemic inflammatory disease classically characterized by intermittent high fevers, an evanescent eruption, polyarthralgia or arthritis, splenomegaly, and laboratory findings of leukocytosis together with negative antinuclear antibody.1 The diagnosis of AOSD can be very difficult and is of exclusion with no specific unified standard. In the present case, the patient developed a high spiking fever, sore throat, leukocytosis, lymphadenopathy, polyarthralgia, and atypical persistent erythematous papules. We performed examinations to exclude infectious diseases, malignancies, and other rheumatic immune diseases. The typical skin presentation of AOSD is an evanescent salmon pink or dark red rash that appears along with the rising of the fever; this presentation has been observed in up to 87% of patients.2 Recently, several case reports have described a few atypical lesions of AOSD, especially a persistent skin rash consisting of pruritic plaques and papules with distinct histopathologic manifestations: single or aggregated areas of dyskeratosis in the upper layers of the epidermis associated with a perivascular inflammatory infiltrate in the upper and mid-dermis, without vasculitis.3-4 Other types of atypical rash have been reported, including urticarial erythema, prurigo pigmentosa-like lesions, diffuse cutaneous mucinosis, and linear hyperpigmentation with increased dermal mucin. In most cases, the atypical skin eruption presents at the time of disease onset concurrently with or shortly after the development of systemic symptoms. These atypical rashes often present together with the typical rash, but they are the only skin manifestation in about 43% of affected patients, leading to high rates of misdiagnosis and missed diagnosis because of under-recognition.5
At present, the treatment of AOSD remains empirical. Glucocorticoid (GC) is considered the first-line of AOSD treatment, can induce a clinical response in about 60% of patients. Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX), azathioprine (AZA) or leflunomide (LEF), are commonly used as second line therapy.6-7 Recently, multiple lines of evidence have suggested the role of biologics in refractory cases, such as anti-IL-1, anti-IL-6 and anti-IL-18 receptor agents, which have proved to be effective to control disease activity and its complications.8-9 Our patient was treated with methyl-prednisolone in combination with methotrexate, and achieved good clinical remission.
In conclusion, the appearance of a persistent atypical rash in patients with AOSD seems to be more frequent than expected, and persistent pruritic papules patho-logically characterized by dyskeratotic keratinocytes may be significantly referable to the diagnosis of AOSD. It is important for dermatologists to recognize these clinical variants to make early diagnosis of AOSD.
. Sun NZ, Brezinski EA, Berliner J, et al Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy. J Am Acad Dermatol 2015;73(2):294–303. doi: 10.1016/j.jaad.2015.04.063.
. Cho YT, Liao YH. Prurigo pigmentosa-like persistent papules and plaques in a patient with adult-onset Still's disease. Acta Derm Venereol 2014;94(1):102–103. doi: 10.2340/00015555-1615.
. Kikuchi N, Satoh M, Ohtsuka M, et al Persistent pruritic papules and plaques associated with adult-onset Still's disease: report of six cases. J Dermatol 2014;41(5):407–410. doi: 10.1111/1346-8138.12426.
. Yoshifuku A, Kawai K, Kanekura T. Adult-onset Still disease with peculiar persistent plaques and papules. Clin Exp Dermatol 2014;39(4):503–505. doi: 10.1111/ced.12335.
. Narváez GFJ, Pascual M, de Recalde ML, et al Adult-onset Still's disease with atypical cutaneous manifestations. Medicine (Baltimore) 2017;96(11):e6318. doi: 10.1097/MD.0000000000006318.
. Giacomelli R, Ruscitti P, Shoenfeld Y. A comprehensive review on adult onset Still's disease. J Autoimmun 2018;93:24–36. doi: 10.1016/j.jaut.2018.07.018.
. Mimura T, Kondo Y, Ohta A, et al Evidence-based clinical practice guideline for adult Still's disease. Mod Rheumatol 2018;28(5):736–757. doi: 10.1080/14397595.2018.1465633.
. Kiltz U, Kiefer D, Braun J, et al Prolonged treatment with Tadekinig alfa in adult-onset Still's disease. Ann Rhemu Dis 2018. doi: 10.1136/annrheumdis-2018-214496.
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