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Hydroxychloroquine for the treatment of lupus erythematosus with cutaneous involvement: clinical efficacy and serial analysis of anti-DNA antibody levels

557 response in June 2019, with no relapse of granulomatosis. Case 2 was a 66-year-old woman who received surgery for a dorsal melanoma in 2015, pT4bN1aM0 (AJCC 2009). In October 2016, she started TT for BRAF-mutant hepatic and pulmonary metastases. In April 2017, fluctuating panniculitis of the lower limbs appeared. In June 2017, a CT scan showing a partial response, revealed interstitial pneumonitis with diffuse ground-glass opacities, subpleural and peribronchovascular nodules, reticulations, and mediastino-hilar nodes. Biological tests, including ACE serum level, immunological tests and quantiferon, and PFT were normal. BAL revealed lymphocytic alveolitis, with negative microbiological investigation. Bronchial biopsies showed non-caseating, sarcoidosis-like epithelioid granulomas. Given the anti-tumoural response and the asymptomatic pulmonary presentation, TT was pursued without corticosteroids. The cutaneous and pulmonary lesions regressed within the subsequent months. In March 2018, the patient had a single relapse of melanoma localized to the brain, which was treated with stereotaxic radiotherapy. In September 2018, she presented with granulomatous panuveitis with macular oedema and diffuse capillaropathy (figure 1D), attested by fundoscopic examination, OCT, and fluorescein and indocyanine green angiography. Given the negative aetiological screen and the failure of local treatments, oral corticosteroids were initiated. After initial improvement, uveitis relapsed as the treatment was tapered, requiring azathioprine. In May 2019, a racemoseinfiltrated livedoid eruption appeared (figure 1E), with polyadenopathy and moderate hypermetabolism on PET TDM, and renal dysfunction. Skin biopsy confirmed the granulomatosis, but renal biopsy was non-contributory. TT was stopped in June 2019 because of flaring granulomatosis and a persistent complete response of the melanoma. The association between malignancy and granulomatoses has been described, especially with melanoma, spontaneously or under antineoplastic therapy [1]. Granulomatosis was reported during treatment with BRAF inhibitors, alone or associated with MEK inhibitors [2, 3], after a median delay of six months, as in our patients [2] with uveitis, lymphadenopathies, myocarditis, and skin nodules or papules [3]. Our cases presented with unusual cutaneous and lung involvement; a livedoid appearance (reported in patients with sarcoidosis, not associated with cancer [4]) and interstitial lung disease with ground-glass opacities. Our first patient received IFN before TT, the involvement of which cannot be excluded [5]. This unusual presentation could be explained by increased serum TNFand IFNlevels during TT [6]. BRAFV600E mutation has a direct role on cell proliferation, and modulates the tumoural microenvironment. Vemurafenib could boost immune-monitoring by increasing IFNproduction and inhibiting Tregs. Thus, sarcoidosis under TT would indicate an anti-tumoural response. In the series reported by Lheure et al., systemic corticosteroid or discontinuation of vemurafenib was not required [2]. Interestingly, our second patient had spontaneous regression of granulomatosis, which relapsed 14 months later, and six months after a localized relapse of melanoma as a granulomatous uveitis requiring oral corticosteroids and azathioprine, as well as TT discontinuation. Immunosuppressive treatment and continuation of the TT should be discussed depending on the benefit/risk evaluation, especially when malignancy is controlled. TT should be pursued as long as possible, given the >50% risk of relapse when discontinued [6-8]. Given these atypical and pleomorphic presentations of granulomatoses, it is important to investigate any clinical or radiological manifestation occurring under TT.