Sarcoid-like granulomatosis in a patient treated by interleukin-1 receptor antagonist for TNF-receptor-associated periodic syndrome

Drug-induced sarcoidosis in a patient treated with an interleukin-1 receptor antagonist for hidradenitis suppurativa

“…Drug-induced sarcoidosis (Table I) may cause polymorphic skin lesions and possible systemic involvement weeks to months after drug initiation 1, 20. Diagnosis of isolated single-organ sarcoidosis or sarcoidlike granulomatosis depends on the evolving definition of sarcoidosis and acknowledgement of a single organ variant 20 .…”

“…Immune checkpoint inhibitors can induce sarcoidosis by modifying cytotoxic, Th1/17 and regulatory T-cell ratios 10, 21Table IDrugs that induce cutaneous sarcoidosis and proposed biologic mechanisms of inductionDrugBiologic mechanismIL-1Ra: anakinra 1 Unopposed type I IFN productionFailure of immune regulatory mechanismsImmunosuppression favoring infection with bacterium implicated in sarcoidosisInterferon-α 3 Induction of Th1 cytokinesanti-TNF agents4, 5: entanercept, 6 infliximab, 7 adalimumab 8 Unopposed type I IFN productionMove toward a Th1/Th17 profileDecreased TNF-mediated suppression of Treg expansion/activityAlteration in ratio of membrane bound to soluble TNFR2Process of anti-IFX antibody productionPredisposition secondary to genetic variation of TNF-α genePD-1 inhibitors: pembrolizumab, 9 nivolumab 10 Increased T-cell proliferative capacityNote: PD-1 up-regulation has also been associated with sarcoidosis with a proposed mechanism of decreased T-cell proliferative capacity leading to immunologic derangements conducive to sarcoidosis BRAF inhibitor: vemurafenib 11 Increased TNF-α and IFN-γ levelsNote: Study suggests patients who have sarcoidosis with vemurafenib therapy carry a better prognosisanti-CTLA4 mAb: ipilimumab 12 Enhanced T-cell responsesanti-IgE mAb: omalizumab 13 Decreased expression of dendritic cell IgE high affinity receptor/Th2 cytokine production with subsequent shift from Th2 to Th1 cytokine profileUnmasking of sarcoidosis with prednisone taper accompanying omalizumab treatment initiationFillers for aesthetic procedures: hyaluronic acid 14 Tissue injury and foreign body reaction to fillerInsulin15, 16Traumatic induction (Koebnerization) and foreign body reaction to materials introduced with insulin injectionInflammatory response to zinc component of insulin formulationBotulinum neurotoxin A 17 Foreign body reaction after deposition of crystalline preparation of botulinum neurotoxin A in the skinForeign body reactio...…”

“…Anakinra, an interleukin (IL)-1 receptor antagonist (IL-1Ra), has only been reported once in the literature to induce sarcoidlike granulomatosis in a patient with TNF receptor–associated periodic syndrome 1 . In this report, IL-1Ra–induced sarcoidal granulomas are postulated to be caused by the upregulation of type 1 IFN and IL-1 cytokine pathway inflammation.…”

Emerging Molecular Targets for the Treatment of Refractory Sarcoidosis

“…We were unable to identify case reports or trials of anakinra use in the treatment of sarcoidosis. However, two cases of anakinra-induced sarcoidosis have been reported (46,47). A phase 2 randomized controlled trial assessing the efficacy and safety of canakinumab, another IL-1 antagonist, in patients with pulmonary sarcoidosis (NCT02888080) has completed the recruitment process.…”

Sarcoidosis Developing During Secukinumab Therapy: Case Report

“…1,3,[5][6][7][8] The relationship of sarcoidosis with TNF-α inhibitors is a dichotomous one, as TNF-α inhibitors both cause and treat sarcoidosis. 1,8,9 Some of these studies have suggested monitoring new agents such as IL-17 and IL-23 inhibitors for similar paradoxical adverse events.…”