Certolizumab-induced sarcoidosis in a patient with psoriatic arthritis - a case report and review of literature.

Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation.

Sarcoidosis-Like Reaction After Chemotherapy Mimicking Metastasis in a Patient With Two Synchronous Tumors: A Case Report.

Sarcoidosis presents a diagnostic challenge due to its diverse clinical manifestations and potential to mimic malignancies. We report a clinical case involving a 46-year-old woman diagnosed with localized synchronous ovarian and endometrial carcinomas treated with surgery. Following adjuvant chemotherapy and radiotherapy, the patient developed suspicious pulmonary micronodules and lymphadenopathy observed in imaging studies, raising concerns about cancer recurrence. Histopathological analysis revealed chronic granulomatous inflammation without evidence of malignancy, leading to a diagnosis of a sarcoidosis-like reaction secondary to chemotherapy. Remarkably, these lesions resolved spontaneously without specific intervention. This case emphasizes the importance of a multidisciplinary approach in managing complex oncological presentations and underscores the significance of histopathological examination in distinguishing between malignancy and chemotherapy-induced sarcoidosis-like reactions.

Drug-induced sarcoidosis-like reaction to adalimumab in the oral mucosa of a patient with Crohn's Disease.

BACKGROUND: The drug-induced sarcoidosis-like reaction (DISR) is a condition clinically and pathologically similar to sarcoidosis but is induced by certain drugs. A few cases of DISR associated with the use of TNF-α antagonists have been reported in the literature. CASE REPORT: A 49-year-old female patient with a diagnosis of Crohn's Disease under treatment with adalimumab presented with a 2-month-long ulcerated swelling in the left lower fornix. Histological analysis of the biopsy specimen revealed multiple non-caseating granulomas multinucleated cells and epithelioid macrophages surrounded by lymphocytes. The lesion is under symptomatic control with a topical corticosteroid, and the patient is being monitored for manifestation in other organs and systems. CONCLUSION: Lesions of DISR may occur isolated in the oral mucosa. Therefore, this complication must be considered in the differential diagnosis of oral granulomatous lesions in patients under treatment with anti-TNF-α drugs.

Successful immunosuppressant-free treatment of a drug-induced sarcoidosis-like reaction caused by dupilumab.

We present a case of a drug-induced sarcoidosis-like reaction (DISR) in a 34-year-old female patient who had been receiving dupilumab for eosinophilic rhinosinusitis, for seven months. Computerized tomography scans revealed multiple lymphadenopathies, and biopsies performed on the lung and skin lesions showed the presence of non-caseating granulomas. The patient's serum levels of soluble interleukin-2 receptor and angiotensin-converting enzyme were elevated. There were no findings of Mycobacterium spp, or any other bacterial infections. Based on these findings, it was suspected that the sarcoidosis-like reaction observed in this patient was caused by dupilumab. Switching the patient's treatment from dupilumab to mepolizumab improved the DISR.

Renal Sarcoidosis-like Reaction Induced by PD-1 Inhibitor Treatment in Non-Small Cell Lung Cancer: A Case Report and Literature Review.

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.

Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination: A case report and review of literature.

BACKGROUND: A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment (S) 5. CASE SUMMARY: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) revealed the nodule in S5 with a defect at the hepatobiliary phase, hyperintensity on diffusion weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC) map. Contrast-enhanced computed tomography revealed hypervascularity at the early phase, and delayed contrast-enhancement was observed at the late phase. Contrast-enhanced ultrasound (US) revealed incomplete defect at the late vascular phase. Inflammatory liver tumor, lymphoproliferative disease, intrahepatic cholangiocarcinoma (small duct type) and bile duct adenoma were suspected through the imaging studies. US guided biopsy, however, showed a noncaseating hepatic sarcoid-like epithelioid granuloma (HSEG), and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells. One month after admission, EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase, of hyperintensity on DWI, of hypointensity on ADC map, and no stain at the early phase. CONCLUSION: That the patient had received BNT162b2 messenger RNA (mRNA) coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG, and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction (DISR) might be induced by the mRNA vaccination. Fortunately, rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

A case of sarcoidosis-like reaction associated with immune checkpoint inhibitors in metastatic renal cell carcinoma.

INTRODUCTION: Immune checkpoint inhibitors are one of the standard treatments for metastatic renal cell carcinoma. Among immune-related adverse events, the sarcoidosis-like reaction is frequently difficult to differentiate from cancer progression. CASE PRESENTATION: A 58-year-old man with renal cell carcinoma with multiple lung metastases was treated with ipilimumab and nivolumab after nephrectomy. Computed tomography after three courses of treatment revealed hilar/mediastinal lymphadenopathies, pleural nodules, and pulmonary interstitial lesions, whereas lung metastases were markedly regressed. Considering positive findings of Gallium scintigraphy and serological tests together, we clinically judged the new lesions as a sarcoidosis-like reaction and continued the treatment until cessation by liver dysfunction. After discontinuation of the immunotherapy, the sarcoidosis-like reaction was regressed without cancer relapse. CONCLUSION: We report here the first case of a clinically diagnosed sarcoidosis-like reaction in metastatic renal cell carcinoma following treatment with immune checkpoint inhibitors.

Sarcoidosis-like reaction after neoadjuvant pembrolizumab combined with chemotherapy mimicking disease progression of NSCLC induced encouraging discovery of pathological complete response.

Neoadjuvant chemoimmunotherapy has demonstrated improved efficacy and prognosis in stage IIa-IIIb patients with non-small cell lung cancer (NSCLC). Drug-induced sarcoidosis-like reaction (DISR), an autoimmune reaction, has been reported as a type of immune-related adverse event that may mimic disease progression. Here, we report the case of patient with NSCLC who developed DISR during neoadjuvant chemoimmunotherapy and finally achieved pathological complete response after surgery.

Adalimumab-induced sarcoidosis-like reaction involving oral cavity in rheumatoid arthritis: a case-based review.

Drug-induced sarcoidosis-like reaction (DISR) is a condition almost indistinguishable from sarcoidosis, both clinically and microscopically, consisting of granulomatous tissue reaction associated with a specific therapy. Commonly affected sites are the lungs, hilar lymph nodes, and skin. This report aimed to describe a very uncommon case of DISR with an unique involvement of the oral cavity. A 63-year-old female with a history of rheumatoid arthritis, who was treated with a TNF-α antagonist (adalimumab), presented multiple ulcerative nodules on the hard palate. Laboratory tests and imaging studies failed to show any other alterations. The biopsy specimen demonstrated multiple noncaseating granulomas. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment highlighted the presence of normal lymphocytes and histiocytes. With the diagnosis of DISR, adalimumab was discontinued, and complete clinical resolution of the lesions was achieved after 14 months. Although uncommon, DISR should be considered in differential diagnoses of oral granulomatous reactions, especially in cases where the patient is being treated with TNF-α antagonists.

Propionibacterium acnes-associated Sarcoidosis Possibly Initially Triggered by Interferon-alpha Therapy.

A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.

Drug-induced sarcoidosis-like reaction in adjuvant immunotherapy: Increased rate and mimicker of metastasis.

BACKGROUND: Anti-[programmed cell death protein 1 (PD-1)] antibodies nivolumab and pembrolizumab were approved for adjuvant treatment of melanoma as they demonstrated improved relapse-free survival. Currently, combined anti-PD-1 plus anti-[cytotoxic T-lymphocyte-associated protein 4 (CTLA4)] blockade is being investigated in adjuvant and neoadjuvant trials. Sarcoidosis-like reactions have been described for immune checkpoint inhibitors and are most likely drug-induced. The reported rate of sarcoidosis/sarcoidosis-like reactions within clinical melanoma trials is <2%. We observed that a remarkably higher number of melanoma patients (10/45 patients, 22%) treated with immune checkpoint inhibitor (ICI) within an adjuvant clinical trial-developed drug induced sarcoidosis-like reaction (DISR) mimicking metastasis. CASE PRESENTATION: Of 45 stage III melanoma patients who were treated at our institute with adjuvant ICI (either nivolumab alone or in combination with ipilimumab) within a two-armed, blinded clinical trial, ten developed a DISR. Three of the ten patients were men, median age was 52 years (range, 32-70 years). DISRs were asymptomatic and generally detected radiographically at first radiographic imaging after the start of therapy (median time, 2.8 months) and described as a differential diagnosis to tumour progression. In one patient, DISR was only apparent 13.1 months after start of therapy and 4 weeks after the end of ICI treatment. DISR presented as mediastinal/hilar lymphadenopathy in 8/10 patients (as only site or in addition to lung, skin and/or bone involvement), one patient had only lung and cutaneous, one patient only cutaneous DISR. Biopsies from lymph nodes, skin and bone were taken in 8/10 patients, and histology confirmed sarcoidosis-like reactions (SLRs). As patients were asymptomatic, no treatment for DISR was required, and study treatment was stopped for DISR in only one patient due to bone involvement. DISRs have resolved or are in remission in all patients. At a median follow-up time of 15.3 months (range, 12-17.6 months), two patients experienced melanoma relapse. CONCLUSIONS: In most cases, sarcoidosis could only be differentiated from melanoma progression on biopsy. Treating physicians as well as radiologists have to be aware of the potentially higher rate of DISR in patients receiving adjuvant ICI. A thorough interdisciplinary workup is required to discriminate from true melanoma progression and to decide on continuation of adjuvant ICI treatment.

Sarcoidosis-like reaction in metastatic triple negative breast cancer treated by anti-PD-L1.

We report the first case of sarcoidosis-like reaction in a patient treated by anti-PD-L1 for a breast cancer. A 69-year-old woman presented with a histologically confirmed lung metastasis of a triple negative breast cancer. She was treated by nab-paclitaxel plus anti-PD-L1 in first line. After 2 months, a dramatic lung response was noticed but an involvement of mediastinal lymph nodes appeared. Endoscopic ultrasound-guided fine-needle aspiration of these lymph nodes revealed multiple epitheloid granulomas without caseating necrosis in favour of a sarcoidosis-like reaction. The patient remained free of symptom and in complete lung response on anti-PD-L1 treatment as a maintenance therapy.

Drug-Induced Sarcoidosis-Like Reactions.

A drug-induced sarcoidosis-like reaction (DISR) is a systemic granulomatous reaction that is indistinguishable from sarcoidosis and occurs in a temporal relationship with initiation of an offending drug. DISRs typically improve or resolve after withdrawal of the offending drug. Four common categories of drugs that have been associated with the development of a DISR are immune checkpoint inhibitors, highly active antiretroviral therapy, interferons, and tumor necrosis factor-α antagonists. Similar to sarcoidosis, DISRs do not necessarily require treatment because they may cause no significant symptoms, quality of life impairment, or organ dysfunction. When treatment of a DISR is required, standard antisarcoidosis regimens seem to be effective. Because a DISR tends to improve or resolve when the offending drug is discontinued, this is another effective treatment for a DISR. However, the offending drug need not be discontinued if it is useful, and antigranulomatous therapy can be added. In some situations, the development of a DISR may suggest a beneficial effect of the inducing drug. Understanding the mechanisms leading to DISRs may yield important insights into the immunopathogenesis of sarcoidosis.