A Comprehensive Review of Sarcoidosis Treatment for Pulmonologists

Background Paradoxical reactions (PRs) are defined as the occurrence during biologic therapy of a pathological condition that usually responds to these drugs. Objectives To estimate the incidence of PRs and identify risk factors. Methods Multicentre study of the database for the Greater Paris University Hospitals, including biologic-naive patients receiving anti-tumour necrosis factor-a, anti-interleukin-12/23, anti-interleukin-17 or anti-a4b7-integrin agents for psoriasis, inflammatory rheumatism or inflammatory bowel disease (IBD). We used natural language processing algorithms to extract data. A cohort and a case-control study nested in the cohort with controls selected by incidence density sampling was used to identify risk factors. Results Most of the 9303 included patients (median age 43Á0, 53Á8% women) presented an IBD (3773, 40Á6%) or a chronic inflammatory rheumatic disease (3708, 39Á9%), and 8489 (91Á3%) received anti-TNF-a agents. A total of 297 (3Á2%) had a PR. The global incidence rate was 7Á6 per 1000 person-years [95% confidence interval (CI) 6Á8-8Á5]. The likelihood of PR was associated with IBD [adjusted odds ratio (aOR) 1Á9, 95% CI 1Á1-3Á2, P = 0Á021] and a combination of at least two inflammatory diseases (aOR 6Á1, 95% CI 3Á6-10Á6, P < 0Á001) and was reduced with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and corticosteroids (aOR 0Á6, 95% CI 0Á4-0Á8, P = 0Á002; and OR 0Á4, 95% CI 0Á2-0Á6, P = 0Á002, respectively). Conclusions The likelihood of PRs was associated with IBD or a combination of a least two inflammatory diseases. More studies are needed to assess the benefit of systematically adding csDMARDs for such high-risk patients.What is already known about this topic?• Most published studies about paradoxical reactions concern paradoxical psoriasis in patients receiving anti-tumour necrosis factor-a agents. • Few data are available for other paradoxical reactions and the most recent biologics.What does this study add?• Risk of paradoxical reactions was increased with inflammatory bowel disease and a combination of at least two inflammatory diseases.

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“…However, several studies have shown the effectiveness of biologics to treat sarcoidosis. [30][31][32]…”

Section: Discussionmentioning

confidence: 99%

“…We decided to include sarcoidosis as a PR even though no biologics are approved for the disease. However, several studies have shown the effectiveness of biologics to treat sarcoidosis 30–32 …”

Section: Methodsmentioning

confidence: 99%

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients

Bataille

Layese

Claudepierre

et al. 2022

British Journal of Dermatology

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“…In a retrospective unblinded uncontrolled cohort study, AZA and MTX yielded similar outcomes [ 47 ]. Reported ADRs are more or less comparable with those of MTX [ 16 ]. Most frequent ADRs include infections, gastro-intestinal complaints, hepatic function decline, pancreatitis, bone marrow depression, as well as fever and fatigue (see also Table 1 ).…”

Section: Second-line Treatmentmentioning

confidence: 99%

“…A recent consensus statement from sarcoidosis experts still endorses glucocorticoids (GCs) as the primary treatment for sarcoidosis, in view of their efficacy and ease of use (low cost and oral administration) [9 ▪ ]. Unfortunately, GCs are associated with a dose-dependent risk of serious ADRs, which tend to accumulate with long-term use (see also Table 1) [1 ▪ ,13–17].…”

Section: First-line Treatmentmentioning

confidence: 99%

Drug-induced comorbidities in patients with sarcoidosis

Drent

Jessurun

Wijnen

et al. 2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewSarcoidosis is a chronic multisystemic inflammatory disease of unknown aetiology with a wide range of highly variable clinical manifestations and unpredictable disease course. Sarcoidosis patients may present with specific organ-related symptoms involving functional impairments, and less specific symptoms. The decision whether and when to treat a sarcoidosis patient with pharmacotherapy depends on two major factors: risk of organ failure and/or death and impairment of quality of life. This decision is complex and not standardized.Recent findingsGlucocorticoids (GCs) are recommended as initial treatment, when needed. Subsequent GC-sparing alternatives frequently follow. Comorbidities or adverse drug reactions (ADRs) from drugs used in sarcoidosis treatment are sometimes very hard to differentiate from symptoms associated with the disease itself, which may cause diagnostic dilemmas. An ideal approach to minimalize ADRs would involve genetic screening prior to prescribing certain ‘high-risk drugs’ and therapeutic drug monitoring during treatment. Pharmacogenomic testing aims to guide appropriate selection of medicines, with the potential of reducing unnecessary polypharmacy while improving clinical outcomes.SummaryA multidisciplinary approach to the management of sarcoidosis may avoid unnecessary ADRs. It is important to consider the possibility of drug-induced damage in sarcoidosis, especially if the clinical situation deteriorates after the introduction of a particular drug.

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“…First-line management for pediatric sarcoidosis includes oral glucocorticoids but the ideal steroid-sparing option is unknown [ 3 ]. Methotrexate, azathioprine, cyclophosphamide, chlorambucil, anti-cytokine biologics and cyclosporine have been utilized in adults with variable efficacy [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Why so low? An unusual case of myositis in a child

et al. 2023

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Background Sarcoidosis is characterized by non-caseating epithelioid granulomas in various tissues throughout the body, most commonly the lung. Non-caseating granulomas may be seen in skeletal muscle, though typically asymptomatic and under-recognized. While rare in children, there is a need to better characterize the disease and its management. Here we present a 12-year-old female with bilateral calf pain who was ultimately found to have sarcoid myositis. Case Presentation A 12-year-old female presented to rheumatology with significantly elevated inflammatory markers and isolated lower leg pain. MRI of the distal lower extremities demonstrated extensive bilateral myositis with active inflammation, atrophy, and to a lesser extent fasciitis. This distribution of myositis in a child garnered a broad differential requiring a systematic evaluation. Ultimately, muscle biopsy revealed non-caseating granulomatous myositis with perivascular inflammation, extensive muscle fibrosis, and fatty replacement of the muscle with a CD4+ T cell predominant, lymphohistiocytic infiltrate consistent with sarcoidosis. Review of histopathology from age 6 of an extraconal mass resected from her right superior rectus muscle further confirmed the diagnosis. She had no other clinical symptoms or findings of sarcoidosis. The patient improved significantly with methotrexate and prednisone, though flared again after self-discontinuation of medications and was subsequently lost to follow-up. Conclusion This is the second reported case of granulomatous myositis associated with sarcoidosis in a pediatric patient, and the first to present with a chief complaint of leg pain. Increased knowledge of pediatric sarcoid myositis within the medical community will enhance recognition of the disease, improve the evaluation of lower leg myositis, and advance outcomes for this vulnerable population.

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A Comprehensive Review of Sarcoidosis Treatment for Pulmonologists

Cited by 17 publications

References 108 publications

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients

Paradoxical reactions and biologic agents: a French cohort study of 9303 patients

Drug-induced comorbidities in patients with sarcoidosis

Why so low? An unusual case of myositis in a child

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