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.

Development of pulmonary sarcoidosis in Crohn's disease patient under infliximab biosimilar treatment after long-term original infliximab treatment: a case report and literature review.

BACKGROUND: Inflammatory bowel disease (IBD) is chronic inflammation of the gastrointestinal tract, although its etiology has largely been unclear. Tumor necrosis factor inhibitors (TNF-I) are effective for the treatment. Recently, biosimilars of TNF-I, such as CT-P13, have been developed and are thought to possess equal efficacy and safety to the original TNF-I. Sarcoidosis is also a systemic granulomatous disease of unknown etiology. In steroid-resistant cases of sarcoidosis, TNF-I have been reported effective for achieving resolution. However, the progression of sarcoidosis due to the TNF-I also has been reported. We herein report a case of pulmonary sarcoidosis with a Crohn's disease (CD) patient developed after a long period administration (15 years) of TNF-I. CASE PRESENTATIONS: A 37-year-old woman with CD who had been diagnosed at 22 years old had been treated with the TNF-I (original infliximab; O-IFX and infliximab biosimilar; IFX-BS). Fifteen years after starting the TNF-I, she developed a fever and right chest pain. Chest computed tomography (CT) revealed clustered small nodules in both lungs and multiple enlarged hilar lymph nodes. Infectious diseases including tuberculosis were negative. Bronchoscopic examination was performed and the biopsy specimens were obtained. A pathological examination demonstrated noncaseating granulomatous lesions and no malignant findings. TNF-I were discontinued because of the possibility of TNF-I-related sarcoidosis. After having discontinued for four months, her symptoms and the lesions had disappeared completely. Fortunately, despite the discontinuation of TNF-I, she has maintained remission. CONCLUSIONS: To our knowledge, this is the first case in which sarcoidosis developed after switching from O-IFX to IFX-BS. To clarify the characteristics of the cases with development of sarcoidosis during administration of TNF-I, we searched PubMed and identified 106 cases. When developing an unexplained fever, asthenia, uveitis and skin lesions in patients with TNF-I treatment, sarcoidosis should be suspected. Once the diagnosis of sarcoidosis due to TNF-I was made, the discontinuation of TNF-I and administration of steroid therapy should be executed promptly. When re-starting TNF-I, another TNF-I should be used for disease control. Clinicians should be aware of the possibility of sarcoidosis in patients under anti-TNF therapy.

Systemic sarcoidosis reactions as a result of tumour necrosis factor-alpha treatment for patients with psoriasis.

The high efficacy and tolerability of biological therapies such as anti-tumour necrosis factor-alpha (TNF-α) have transformed outcomes for many inflammatory conditions. Conversely, a wide range of paradoxical reactions, including pulmonary, renal and ocular sarcoidosis secondary to TNF-α blocking agents in patients with severe psoriasis, has been reported. Sarcoid-like granulomatosis is one of these reactions, which may affect the pulmonary and cutaneous systems. Renal and ocular sarcoidosis, however, are less frequent and have unknown consequences. In this report, we present two cases of anti-TNF-α-induced sarcoidosis involving the pulmonary and renal systems.

[socioecological features of the epidemiology of sarcoidosis in the poltava region, Ukraine].

OBJECTIVE: Introduction: Lung sarcoidosis is a systemic granulomatous disease that can affect various organs and systems of a person. Due to the lack of a uniform standardized approach to the diagnosis of sarcoidosis, the epidemiological pattern is heterogeneous and depends on many factors. The aim: To investigate the correlation between the number of patients with sarcoidosis among the population of the Poltava region (Ukraine) and the ecological characteristics of the industrial activity of the region in comparison with the data on the availability of subspecialists in respiratory diseases. PATIENTS AND METHODS: Materials and methods: The study is based on a retrospective analysis of patients with sarcoidosis living in the Poltava region (Ukraine) for the period from 2008 to 2018. RESULTS: Results: The analysis of the correlation between the intensity of environmental impacts on the region and the number of patients with sarcoidosis did not reveal statistically significant changes. An odds ratio (OR) of the occurrence of sarcoidosis among the urban population has not experienced significant dynamics (OR 1,337, 95% CI: 0.96-1.86) compared with those living in rural areas. The number of specialists performing the duties of a pulmonologist in the region is associated with a significantly higher number of registered patients with various forms of sarcoidosis (r=0.27, p=0.04). CONCLUSION: Conclusions: There was no reliable relationship between the risk of sarcoidosis and habitat in areas with increased ecological and industrial load in the Poltava region. The uneven distribution of specialized medical care reduces the patient's odds of establishing a diagnosis of sarcoidosis in the countryside.

EBUS-TBNA Can Distinguish Sarcoid-Like Side Effect of Nivolumab Treatment from Tumor Progression in Non-Small Cell Lung Cancer.

With the expansion of immunotherapy in the treatment of lung cancer, clinicians have to face new clinical pictures and adapt their practice. We report the case of a 69-year-old man diagnosed with non-small cell lung cancer using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and treated with nivolumab as second-line therapy. After 8 injections of nivolumab, a new CT and PET scan revealed massive growth and increase in metabolism of hilar and mediastinal lymph nodes, whereas the size and metabolism of the left upper lobe lesion were reduced. A new EBUS-TBNA was thus performed and showed an epithelioid cell reaction compatible with sarcoidosis in the 3 punctured lymph nodes (stations 4R, 11L, 7). In the absence of cancer evolution, nivolumab was continued, and the CT after the twelfth injection showed stability.

Adalimumab-induced pulmonary sarcoidosis not progressing upon treatment with etanercept.

Tumor necrosis factor alpha (TNF-α) inhibitors effectively treat sarcoidosis, but can, paradoxically, induce sarcoidosis. The TNF-α inhibitor etanercept is most commonly associated with paradoxical sarcoidosis, which has previously been reported to be resolved by adalimumab. However, we describe the case of a patient with ankylosing spondylitis and adalimumab-induced sarcoidosis not aggravated by switching to etanercept, thus indicating that etanercept could be a treatment option for patients who develop paradoxical sarcoid-like reactions after treatment with other TNF-α inhibitors.

[Sarcoid-like granulomatosis in patients treated with anti-TNFα]. / LE CAS CLINIQUE DU MOIS. Granulomatose sarcoïdose-like chez les patients traités par anti-TNFα.

Over recent years, anti-TNFα have been used to treat rheumatoid arthritis. The principal secondary effect of anti-TNFα is tuberculosis infections. Another paradoxical effect, previously less well understood, is the development of sarcoid-like granulomatous reactions. We report the case of a 36 year old woman who had been treated for 9 years with anti-TNF alpha. She developed a pulmonary sarcoid-like gra-nulomatosis, complication that is rare but not exceptional in patients treated with TNF-blockers. Discontinuation of anti TNF usually led to recovery. It has been suggested that these reactions mainly occur with etanercept, but this requires further confirmation.

Genetic susceptibility to beryllium: a case-referent study of men and women of working age with sarcoidosis or other chronic lung disease.

OBJECTIVE: The study was designed to investigate whether beryllium exposure was related to illness diagnosed as sarcoidosis. Chronic beryllium disease (CBD) and sarcoidosis are clinically and pathologically indistinguishable, with only the presence of beryllium-specific T-lymphocytes identifying CBD. Testing for such cells is not feasible in community studies of sarcoidosis but a second characteristic of CBD, its much greater incidence in those with a glutamic acid residue at position 69 of the HLA-DPB1 gene (Glu69), provides an alternative approach to answering this question. METHODS: Cases of sarcoidosis aged 18-60 years diagnosed in Alberta, Canada, from 1999 to 2005 were approached through their specialist physician, together with age-matched and sex-matched referents with other chronic lung disease. Referents were grouped into chronic obstructive pulmonary disease (COPD), asthma and other lung disease. Participants completed a telephone questionnaire, including industry-specific questionnaires. DNA was extracted from mailed-in mouthwash samples and genotyped for Glu69. Duration of employment in types of work with independently documented beryllium exposure was calculated. RESULTS: DNA was extracted for 655 cases (270 Glu69 positive) and 1382 referents (561 positive). No increase in sarcoidosis was seen with either Glu69 or beryllium exposure (none, <10, ≥10 years) as main effects: longer duration in possible beryllium jobs was related to COPD. In Glu69 positive men with exposure ≥10 years, the trend towards increasing rate of COPD was reversed, and a significant interaction of duration of exposure and Glu69 was detected (OR=4.51 95% CI 1.17 to 17.48). CONCLUSIONS: The gene-environment interaction supports the hypothesis that some cases diagnosed as sarcoidosis result from occupational beryllium exposure.

Pulmonary sarcoidosis and latent tuberculosis in a patient with psoriasis treated with adalimumab.

Tumor necrosis factor (TNF) inhibitors are powerful biologic medications that have been used successfully in the treatment of a variety of inflammatory conditions, including psoriasis. Although TNF inhibitors are generally well tolerated, their use increases the risk of infections such as tuberculosis (TB), and paradoxically, they have been associated with development of sarcoidosis. We report the case of a 54-year old man with plaque psoriasis who developed a positive TB test and pulmonary sarcoidosis after 12 months of adalimumab treatment. After stopping adalimumab, his psoriasis worsened and he was started on ustekinumab and narrowband UVB, with improvement in symptoms. We provide a review of the literature and discuss treatment challenges.

Interferon beta-related nephropathy and interstitial lung disease: a new association and a long-term warning.

We report on a so-far never described association between glomerulonephritis and sarcoid-like lung disease after long-term interferon beta (IFNb) treatment for relapsing-remitting multiple sclerosis. The interest in this case resides in the documented remission after IFNb discontinuation. The history of IFNb-related adverse events is probably not yet completely written. The rapid reversal of the pathological signs in our patient underlines the importance of careful clinical and laboratory surveillance, including kidney functional parameters, for an early diagnosis of IFNb-related diseases.

Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage M1 activation.

Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated receptor gamma (PPARγ) knock out mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPARγ knock out alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPARγ knock out mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPARγ-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis.

[Establishment and identification of a C57B/6 mouse sarcoidosis granuloma model].

OBJECTIVE: To establish a C57BL/6 mouse sarcoidosis granuloma model elicited by mycobacterial superoxide dismutase A peptide (SodA). METHODS: Thirty female C57BL/6 mice were randomly divided equally into 5 groups: a combination (SodA+Sepharose) group, a SodA group, a IFA (incomplete Freund's adjuvant) group, a sepharose group and a blank control group. On the first day, the combination group and the SodA group were sensitized by subcutaneous injection of 50 µg SodA incorporated into IFA 0.25 ml. The IFA group and the Sepharose group were treated with subcutaneous injection of IFA 0.25 ml and PBS 0.25 ml respectively, while the blank control group was not given any treatment. On the 14th day, the combination group was challenged by tail vein injection of 50 µg SodA covalently coupled to 6000 agarose 4B beads (in PBS 0.5 ml) . The SodA group was challenged by tail-vein injection of 50 µg SodA (in PBS 0.5 ml) . The IFA group and the Sepharose group were treated by tail-vein injection of 6000 agarose 4B beads (in PBS 0.5 ml) , while the blank control group was not given any treatment. On the 22th day, the mice were dissected and the gross and pathological changes of lymph nodes and lungs were observed. Immunohistochemisty was used to identify Mac-2 and CD(+)4T in granuloma. Counts and differentials of BALF cells were measured. CD(+)4/CD(+)8 in BALF and cytokines (IFN-γ and IL-12 ) levels in the lungs were detected by flow cytometry. RESULTS: Enlargement of peripheral and pulmonary hilar lymph nodes were found in the combination group and the SodA group, and sarcoidosis granuloma was found in the lymph nodes and lungs of the combination group. Sarcoidosis granuloma was also found in the lymph nodes but not in the lungs of the SodA group. No sarcoidosis granuloma was observed in the lungs and lymph nodes of the IFA group, the Sepharose group and the blank control group. Macrophage specific antigen Mac-2 and CD(+)4T were positive in the core and rim of the granuloma respectively. The lymphocyte percentages in the BALF of the combination group and the SodA group [(19.4 ± 6.5)% and (22.3 ± 8.5)%] were significantly higher than that in the IFA group, the Sepharose group and the blank control group [(8.5 ± 4.3)%, (7.7 ± 3.4)%, (0.8 ± 0.6%)] (P < 0.05 ). CD(+)4/CD(+)8 in the BALF of the combination group and the SodA group (3.5 ± 1.4, 3.2 ± 1.1) were significantly higher than that in the IFA group and the Sepharose group (1.2 ± 0.5, 1.0 ± 0.4) (P < 0.05 ). IFN-γ and IL-12 in the lungs of the combination group and the SodA group [IFN-γ:(32.9 ± 9.7) ng/L, (26.4 ± 7.2) ng/L; IL-12: (29.6 ± 9.4) ng/L, (26.1 ± 8.9) ng/L]were significantly higher than those of the IFA group, the Sepharose group and the blank control group [IFN-γ: (16.5 ± 6.8) ng/L, (12.2 ± 5.0) ng/L, (9.0 ± 2.6) ng/L; IL-12: (16.7 ± 4.6) ng/L, (13.6 ± 4.4) ng/L, (9.6 ± 5.3) ng/L] (P < 0.05 ). But these indexes were not significantly different between the combination group and the SodA group, and among the IFA group, the Sepharose group and the blank control group (P > 0.05). CONCLUSION: SodA can elicit sarcoidosis granuloma in C57BL/6 mice, and the immunological features of the model were similar to those in human sarcoidosis.

Pulmonary sarcoidosis-like reactions induced by sintilimab in esophageal cancer: A case report.

RATIONALE: Esophageal cancer is one of the deadliest cancers in the world, with high incidence and mortality rates ranking among the top ten in China. The efficacy of conventional treatments is limited and often accompanied by severe adverse reactions, which results in unsatisfactory outcomes. The mechanism of immune checkpoint inhibitors (ICIs) is to activate cytotoxic T cells to kill tumor cells expressing tumor antigens. The application of ICIs has profoundly changed the mode of cancer treatment. However, the use of ICIs also induces a series of adverse reactions similar to autoimmune reactions, called immune-related adverse events (irAEs). Some ICIs can cause manifestations similar to those in the development of sarcoidosis, which are called sarcoidosis-like reactions or granulomatosis. PATIENT CONCERNS: We report a 50-year-old Chinese male patient. DIAGNOSES: The patient had been diagnosed with advanced esophageal squamous cell carcinoma , and was confirmed to have pulmonary sarcoidosis-like reactions associated with sintilimab, a human programmed cell death protein 1 (PD-1) inhibitor. INTERVENTIONS: The patient was administered corticosteroid treatment. OUTCOMES: After receiving steroid treatment, the patient's systemic and pulmonary symptoms improved rapidly. To our knowledge, this is the first report of pulmonary sarcoidosis-like reaction in a patient with esophageal squamous cell carcinoma. The patient then continued to receive 1 year of follow-up antitumor treatment after the appearance of lung pulmonary sarcoidosis-like reactions. The prognosis was good and the patient's condition is currently stable. LESSONS: The diagnosis of ICI-induced sarcoidosis often requires comprehensive evaluation through clinical, pathological, and radiological assessment. A subset of patients with sarcoidosis-like reactions may not require treatment unless there is organ dysfunction or severe clinical symptoms, and these reactions generally respond well to treatment. The occurrence of sarcoidosis-like reactions after immunotherapy is positively correlated with the long-term prognosis of cancer patients. However, this hypothesis requires larger prospective studies for validation.

Etanercept-induced cutaneous and pulmonary sarcoid-like granulomas resolving with adalimumab.

A 59-year-old female with rheumatoid arthritis on etanercept therapy presented with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules subsequently developed on the upper and lower extremities. Except for a new cough, the patient was systemically well. Biopsy of the mass showed sarcoidal type granulomatous inflammation with nodular aggregations of non-necrotizing epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept was discontinued, and the patient was started on adalimumab for rheumatoid arthritis control. The cutaneous nodules fully resolved in 6 months with no additional treatment. A 4-month follow-up CT scan showed significant regression of mediastinal adenopathy. The patient has since been maintained on adalimumab therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic response modifiers targeting tumor necrosis factor alpha (TNFα) are effective treatments of chronic inflammatory conditions such as rheumatoid arthritis and psoriasis. TNFα represents a major cytokine in granuloma formation, and TNFα inhibitors are sometimes efficacious in the treatment of sarcoidosis. Paradoxically, there is a small volume of literature implicating TNFα inhibitors in the development of sarcoid-like disease. We present this case to promote the recognition of TNFα inhibitor-induced sarcoidosis and to illustrate the wide clinicopathologic differential of sarcoidal type granulomas.

Tunnel excavation triggering pulmonary sarcoidosis.

CONTEXT: A definite cause of sarcoidosis has not been identified, however past research suggests that environmental factors may be triggers of the granulomatous response in genetically susceptible individuals. CASE PRESENTATION: A 22-year-old male non-smoker, presented with progressive exertional dyspnea and cough of 3 months duration. One year before, when he started working in tunnel excavation, he had a normal chest radiograph. Chest imaging revealed bilateral nodules and masses of peribronchovascular distribution plus mediastinal lymphadenomegaly. Histologic lymph node analysis revealed non-caseating confluent granulomas. Sarcoidosis was diagnosed. The patient was treated with corticosteroids and advised to change jobs. Complete remission of the disease was achieved and persisted for at least one year without steroid treatment. DISCUSSION: Sarcoidosis is believed to have environmental triggers. The timing of the onset of sarcoidosis in this patient following intensive exposure to tunnel dust suggests an environmental contribution. The recognition that sarcoidosis may have occupational triggers have medical, employment, and legal implications.

COVID-19-induced pulmonary sarcoid: A case report and review of the literature.

BACKGROUND: The COVID-19 pandemic has resulted in dramatic loss of life worldwide, but as the large number of acutely ill patients subsides, the emerging group of "COVID-19 long-haulers" present a clinical challenge. Studies have shown that many of these patients suffer long-term pulmonary disease related to residual fibrosis. Prior studies have shown that while many patients have non-specific findings of fibrotic-like changes, others develop specific patterns of interstitial lung disease. CASE REPORT: Here, we present the first case of a patient developing pulmonary sarcoidosis one year after critical illness from COVID-19. He developed numerous non-necrotizing and well-formed granulomas in mediastinal lymph nodes and pulmonary nodules, compatible radiographically and pathologically with sarcoid. CONCLUSIONS: While the pathophysiology of sarcoid is incompletely understood, inflammation is mediated through the dysregulation of a number of different cytokines (IFNγ, IL-2, IL-12, IL-17, IL-22). This case provides valuable clues for better understanding of the shared pathophysiology of cytokine dysregulation seen in COVID-19 and other interstitial lung diseases such as sarcoidosis.

Pembrolizumab-Associated Cutaneous and Pulmonary Sarcoidosis in Non-Small Cell Lung Cancer Treatment.

Immune checkpoint inhibitor (ICI) therapy has reshaped the treatment landscape in many cancers including non-small cell lung cancer (NSCLC). ICI-therapy can lead to a diverse array of immune-related adverse effects (irAEs), and prompt recognition and management are key to successful treatment. With wide-spread use of ICI therapy in clinical practice, rare irAEs are being increasingly recognized. This report documents a patient with advanced NSCLC who developed pembrolizumab-associated sarcoidosis with multiorgan involvement. Multidisciplinary management led to timely diagnosis and treatment, leading to improvement in symptoms. This case raises awareness of sarcoidosis as a rare side effect of pembrolizumab.

Sarcoidosis complicating treatment with natalizumab for Crohn's disease.

Natalizumab is a humanised monoclonal antibody targeting the lymphocyte adhesion molecule a4 integrin, with proven efficacy in multiple sclerosis (MS) and Crohn's disease (CD). The development of sarcoidosis with extrapulmonary involvement is reported in two patients with refractory CD who had received maintenance therapy with natalizumab. This complication has not been previously reported. It is hypothesised that the effect of natalizumab in altering lymphocyte mucosal trafficking may underlie the development of sarcoidosis in these patients.