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

Abstract

Sarcoidosis and sarcoid‐like reactions (SLRs) may develop in association with various malignancies, as well as in association to certain oncologic drugs, including immune checkpoint inhibitors (ICIs). We aimed to perform a narrative review with regard to the development of ICIs‐associated sarcoidosis or SLRs, and to discuss the corresponding diagnostic and therapeutic challenges raised in this scenario. Apropos of a melanoma patient developing SLRs while treated with ipilimumab and nivolumab, we searched for clinically evident, ICIs‐associated sarcoidosis or SLRs in the English literature. We recorded the oncologic characteristics, including type of malignancy and type of ICI, the phenotypic characteristics of sarcoidosis/SLRs, as well as the impact on immunotherapy. Including our patient, we identified 80 ICIs‐associated sarcoidosis or SLRs cases. Both sexes were equally affected (40 F/40 M) and the most common malignancy was melanoma (65/80, 81.3%). Concerning the oncologic treatment, there was a predilection for pembrolizumab (23/80, 28.7%), followed by the ipilimumab/nivolumab combination (21/80, 26.3%), ipilimumab (18/80, 22.5%), nivolumab (16/80, 20.0%). Although in the majority of the cases (52/80, 65.0%) there was no need for systemic prednisolone for the management of sarcoidosis, a significant proportion of patients finally discontinued ICIs treatment (44/80, 55.0%). Phenotypically, sarcoidosis and SLRs highly imitate oncologic progression posing diagnostic difficulties. A therapeutic dilemma is also raised when there is a need for systemic prednisolone, since the latter may jeopardize the therapeutic efficacy of immunotherapy. Sarcoidosis and SLRs, though rare, can present in oncologic patients treated with ICIs. Clinicians should be aware of this possibility and the related diagnostic and therapeutic challenges they have to face in this scenario.

European recommendations for management of immune checkpoint inhibitors‐derived dermatologic adverse events. The EADV task force ‘Dermatology for cancer patients’ position statement

“…In all cases, management of such AE should always be discussed in a multi‐disciplinary way, involving a dermatologist. Whereas pulmonary granulomata and hilar/mediastinal lymphadenopathy are a well‐established irAE, cutaneous granulomatous/sarcoid‐like eruptions (GE) have been also described in the context of ICI treatment 99,100 …”

“…Eighty cases of ICI‐induced GE have been reported with both anti‐CTLA‐4, anti‐PD‐1 or in combination, and mostly in patients with melanoma. Exclusive cutaneous/subcutaneous involvement is uncommon, noted in only 8/80 patients 99,100 . The median time of onset is 6 months 100 .…”

“…• Whereas pulmonary granulomata and hilar/mediastinal lymphadenopathy are a well-established irAE, cutaneous granulomatous/sarcoid-like eruptions (GE) have been also described in the context of ICI treatment. 99,100 Eighty cases of ICI-induced GE have been reported with both anti-CTLA-4, anti-PD-1 or in combination, and mostly in patients with melanoma. Exclusive cutaneous/subcutaneous involvement is uncommon, noted in only 8/80 patients.…”

“…Exclusive cutaneous/subcutaneous involvement is uncommon, noted in only 8/80 patients. 99,100 The median time of onset is 6 months. 100 The most common site of skin involvement is upper and lower extremities.…”

Skin Manifestation Induced by Immune Checkpoint Inhibitors

“…By contrast, exclusive cutaneous involvement was observed only in 10% (8/80). 56 Clinically, subcutaneous erythematous nodules, papulonodules, plaques, and annular erythematous lesions are presented ( Figure 9A and B ). Some cases such as infiltrative erythema do not fit into any type of cutaneous sarcoidosis, and are reported under the term of sarcoidosis-like, sarcoid reaction, or sarcoidal granulomatous dermatitis.…”