Cutaneous sarcoidosis in a melanoma patient under Ipilimumab therapy

Abstract

A 46-year-old woman was diagnosed in 2013 with a choroid melanoma treated with plaque brachytherapy. A year later, metastatic disease in the liver was confirmed with biopsy and chemotherapy with Dacarbazine was administered. After three cycles, a computerized tomography (CT) evidence disease progression in the liver and therapy with the anti-CTLA4 antibody, Ipilimumab, was started (Dose: 3 mg/Kg. Total dose per cycle: 180 mg). One week after the fourth administration, the patient was remitted to our department because of generalized pruritus and cutaneous lesions on the lower limbs. Clinical examination revealed bilateral and symmetrical erythematous pretibial plaques and nodules (FIG. 1). Both lesions were biopsied, and pathology showed noncaseating granulomas in the dermis consistent with sarcoidosis (FIG. 2). Blood tests revealed an increased angiotensin-converting enzyme (107 U/L. Normal range, 8-52 U/L). The pretibial plaques were treated with topical clobetasol with a significant improvement. During radiological follow-up progression of the liver metastatic disease was detected and administration of Ipilimumab was stopped following the induction therapy, replacing the treatment.The patient is now participating in a new clinical trial. One month after discontinued Ipilimumab she reported progressive dyspnea. CT showed a new nodule on the right lower lobe and fibrous tracts and functional lung tests revealed severe decrease in carbon monoxide diffusing capacity (20% of predicted value). A bronchoscopy was normal and the broncho-alveolar lavage showed lymphocytosis with an inverted CD4:CD8 ratio (0.36). Although the CD4/CD8 ratio is usually high in pulmonary sarcoidosis, it was decided to initiate treatment with oral corticosteroids. After a few days the patient showed clinical improvement without relapse of dyspnea until now. DiscussionIpilimumab is a humanized monoclonal antibody against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) which has proved to increase survival in patients with metastatic melanoma (1). CTLA-4 is a negative regulator of T-cell activation so its blockade is thought to enhance an antitumor immune response. Its mechanism of action may be responsible for autoimmune adverse events like enterocolitis, hypophysitis, dermatitis, uveitis, vitiligo, arthritis, or hepatitis. A recent systematic review and meta-analysis tried to assess the incidence and nature of immune related adverse events associated with anti-CTLA-

Sarcoid-like Granulomatosis Associated with Immune Checkpoint Inhibitors in Melanoma

“…A total of 183 articles matched the search equation. Of these, 45 were related to cases of granulomatosis occurring during ICI treatment for melanoma with information on oncologic follow-up [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. A total of 67 patients were described, with a majority of men (55%) and a mean age at diagnosis of melanoma of 58 years.…”

Challenges in sarcoidosis and sarcoid‐like reactions associated to immune checkpoint inhibitors: A narrative review apropos of a case

“…Table 1 summarizes the studies reporting clinically evident sarcoidosis and SLRs related to ICIs therapy, published in the English literature so far, including information about the type of malignancy, type of ICI, sarcoidosis phenotype, type of treatment and survival of ICI. Including our patient, we were able to identify 80 individuals developing sarcoidosis or SLR in association to ICIs treatment 3‐54 . Based on these records, both sexes were equally affected (40 M/40F), whilst by far the most common malignancy was melanoma (65/80, 81.3%), with only 15 of 80 cases (18.8%) being other than melanoma tumors.…”

Cutaneous Adverse Events of Immune Checkpoint Inhibitors: A Literature Review

“…Furthermore, de-novo development or exacerbation of preexisting sarcoidosis, urticaria, rocasea, or prurigo simplex/ nodularis, may occur [22,60,61]. Sarcoidosis is not uncommon and its clinical presentation may vary from papules or plaques to erythema nodosum, with or without pulmonary or other organ involvement [62][63][64][65]. Systemic or topical steroids may be applied for the treatment of the skin lesions.…”