Paraneoplastic adult-onset Still’s disease in a patient with lung cancer

Dear Editor, Adult-onset Still's disease (AOSD), a systemic inflammatory disorder, frequently poses diagnostic challenges.[1,2] Conducting a comprehensive cancer survey is essential, as patients with cancer and AOSD symptoms may receive a diagnosis of paraneoplastic AOSD.[1,3] Solid cancers, particularly breast and lung cancer and hematopoietic malignancies like lymphoma, are frequently associated with paraneoplastic AOSD.[3] In this report, we present a case where AOSD features manifested as the initial paraneoplastic sign of lung cancer. A 57-year-old otherwise healthy female presented to our dermatology department with persistent pruritic skin rash, periodic spiking fever, sore throat, and arthralgia for 6 months. Initially, she was diagnosed with eczematous dermatitis and was treated with topical corticosteroids with minimal improvement. Physical examination revealed salmon-pink maculopapules and plaques with a linear distribution on the neck, chest, and abdomen, as well as flagellate erythema on the back [Figure 1a-c]. Histopathological examination obtained from the abdomen demonstrated dispersed dyskeratotic keratinocytes in the upper epidermis and perivascular lymphocytic infiltration in the upper dermis [Figure 1d]. Laboratory examination showed elevated white blood cell count (14,100/uL, reference 3900–10,600/uL), normal segment percentage (72.3%, reference 42%–74%), elevated liver function tests, including aspartate aminotransferase (68 U/L, reference 13–40 U/L), alanine transaminase (56 U/L, reference 7–40 U/L), and hyperferritinemia (4158 ng/mL, reference 30–400 ng/mL). Autoimmune surveys, including antinuclear antibody (ANA) and rheumatoid factor (RF), yielded negative results. The patient denied chest or abdominal discomfort and lymphadenopathy.Figure 1: Clinical findings of adult-onset Still's disease-like paraneoplastic syndrome. (a) Salmon-pink maculopapules and plaques with linear configuration on the chest and abdomen. (b) Flagellate erythema on the back. (c) Close-up view of papules and plaques on the left abdomen. (d) Histopathology showing dispersed dyskeratotic keratinocytes in the upper epidermis and perivascular lymphocytic infiltration with scattered neutrophils in the upper dermis (H and E, ×200). (arrowhead, dyskeratotic keratinocytes).The clinical presentation closely resembled AOSD and fulfilled the Yamaguchi criteria, including four major criteria (fever ≥39°C for at least 1 week, arthralgia or arthritis for at least 2 weeks, salmon-colored rash on the trunk, leukocytosis) and two minor criteria (sore throat, abnormal liver function tests, and negative tests for ANA and RF).[1] In accordance with Fautrel's criteria, the patient met four major criteria (spiking fever ≥39°C, arthralgia, transient erythematous rash, and sore throat) and two minor criteria (maculopapular rash and leukocytosis ≥10,000/mm3).[1] Given the potential association between AOSD symptoms and malignancies, a comprehensive cancer survey was performed. Chest computed tomography and needle biopsy confirmed the presence of left lower lung adenocarcinoma with mediastinal lymph node metastasis. Following the diagnosis, the patient received chemotherapy with pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) in conjunction with corticosteroid therapy (0.5 mg/kg per day). The patient's skin rash regressed in correlation with each course of chemotherapy, showing temporal associations with the severity of lung cancer disease. During the 6-month follow-up, her lung cancer remained stable, and other systemic symptoms, including fever, arthralgia, and sore throat, improved concomitantly with the resolution of the skin rash [Figure 2].Figure 2: Clinical findings of the same patient 6 months after chemotherapy. (a) Regression of maculopapules on the chest and abdomen. (b) Regression of flagellate erythema on the back.AOSD is typically characterized by quotidian spiking fever, maculopapular rash, and arthritis.[2] Other manifestations may include liver dysfunction, sore throat, and cardiopulmonary involvement.[4] The most common cutaneous feature is an evanescent, salmon-pink maculopapular rash during febrile attacks, while variable skin manifestations have been reported, including flagellate erythema, eczematous lesions, and fixed plaques.[4] Some lesions present as persistent pruritic eruption of linear-shaped papules and plaques with scales or crusts, a condition initially described in 2005.[5,6] Histopathologically, the evanescent rash is characterized by a superficial perivascular infiltrate of lymphocytes and neutrophils, while the persistent pruritic eruption shows solitary or cluster dyskeratotic keratinocytes in the upper epidermis.[5] The diagnostic criteria proposed by Yamaguchi and Fautrel have been proven to be valuable tools for the diagnosis of AOSD, exhibiting 94% sensitivity and 99% specificity, respectively.[1,2] Notably, hyperferritinemia can be detected and serves as a helpful marker for confirmation of AOSD.[2] To establish a definitive diagnosis of AOSD, a thorough diagnostic work-up is essential to rule out malignant, infectious, or rheumatic etiologies. In paraneoplastic AOSD, pro-inflammatory cytokines, such as interleukin (IL)-18 produced in cancer cells or systemic reactions, along with IL-6 released by macrophages, may contribute to the pathogenesis of systemic symptoms.[3] In some cases, successful tumor therapy has resulted in the resolution of AOSD symptoms.[7] Acute AOSD management often involves corticosteroids or nonsteroid anti-inflammatory drugs, with steroid-sparing agents such as methotrexate, azathioprine, or cyclosporine as adjunctive therapies.[8] In our case, diligent serial examinations ultimately revealed an underlying malignancy, facilitating the initiation of appropriate anticancer and corticosteroid treatments. Consequently, we confirmed a diagnosis of paraneoplastic AOSD secondary to lung cancer. Our case highlights the characteristic features of AOSD, including a salmon-colored rash, flagellate erythema, fever, sore throat, and arthralgia, along with distinctive histopathological findings of persistent pruritic eruption such as dyskeratotic keratinocytes in the upper epidermis. Thorough screenings for cancer, infections, and autoimmune conditions are crucial for clinical physicians to unveil hidden malignancies, as demonstrated in our case, enabling precise therapeutic strategies. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Data availability statement Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest Dr. Wei-Ti Chen, an social media editor at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.