Search

Background: Sarcoidosis is a multi-system disorder with an increasing propensity to present in older patients. Diagnostic uncertainty is common and understandable given the higher prevalence of co-morbidities in older patients and broad differential for multi-system clinical presentations. Excluding malignancy and infection with a high degree of certainty is challenging and may require repeated confirmatory investigation where the diagnosis remains in doubt., Summary of Main Findings: There are a paucity of studies examining late-onset sarcoidosis. Female predominance, pulmonary, ocular, skin and systemic symptoms are common, while more classical presentations such as Lofgren's syndrome are uncommon. Positivity rates of biopsies vary between studies; however, targeted biopsies of accessible sites with organ involvement are the most successful. Therapeutic management is directed at reducing inflammation, and thereby reducing symptom burden, improving quality of life and avoiding progression of organ damage. While most older patients will require corticosteroid therapy, they are also more prone to developing adverse effects. Most older patients will experience a clinical remission; however, the risk of developing chronic sarcoidosis and organ damage is higher compared with younger counterparts. Patients with evidence of pulmonary fibrosis and pulmonary hypertension are at particular risk., Impact on Clinical Practice: Health care providers who care for older adults should be aware of the increasing prevalence of late-onset sarcoidosis and consider the diagnosis in those who present with otherwise unexplained systemic symptoms, thoracic abnormalities on imaging and/or evidence of other organ involvement. Earlier diagnosis and therapeutic intervention to halt the development of pulmonary fibrosis and pulmonary hypertension and monitoring for treatment-related adverse effects will confer a mortality benefit., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pulmonary sarcoidosis is characterized by an exaggerated CD4 + T cell response and formation of non-necrotizing granulomas. Tumour necrosis factor α (TNF-α) is regarded as crucial for granuloma formation and TNF-α inhibitors offer a third-line treatment option for patients not responding to conventional treatment. However, not all patients benefit from treatment, and an optimal dose and treatment duration have not been established. Insight into the influence of TNF-α inhibitors on lung immune cells may provide clues as to what drives inflammation in sarcoidosis and improve our understanding of treatment outcomes. To evaluate the effects of treatment with the TNF-α inhibitor infliximab on lung immune cells and clinical features of the patients, 13 patients with sarcoidosis refractory to conventional treatment were assessed with bronchoalveolar lavage (BAL), spirometry and computerized tomography (CT) scan closely adjacent to the start of infliximab treatment. These investigations were repeated after 6 months of treatment. Treatment with TNF-α inhibitor infliximab was well tolerated with no adverse events, except for one patient who developed a probable adverse event with liver toxicity. Ten patients were classified as responders, having a reduced CD4/CD8 ratio, a decreased percentage of CD4 + T cells expressing the activation marker CD69 and number of mast cells (P < 0·05 for all). The percentage of T regulatory cells (T regs ), defined as forkhead box P3 + CD4 + T cells decreased in most patients. In conclusion, six months of infliximab treatment in patients with sarcoidosis led to signs of decreased CD4 + T cell alveolitis and decreased mastocytosis in the lungs of responders., (© 2020 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)

Lymphocytes play a crucial role in lung inflammation. Different interstitial lung diseases may show distinct lymphocyte activation profiles. The aim of this study was to examine the expression of a variety of activation markers on T lymphocyte subsets from blood and bronchoalveolar lavage fluid (BALF) of patients with different granulomatous interstitial lung diseases and healthy controls. Bronchoalveolar lavage cells and blood cells from 23 sarcoidosis patients, seven patients with hypersensitivity pneumonitis and 24 healthy controls were analysed. Lymphocyte activation status was determined by flow cytometry. Lymphocytes were stained with antibodies against CD3, CD4, CD8, CD25, CD28, CD69, very late antigen-1 (VLA)-1, VLA-4 and human leucocyte antigen D-related (HLA-DR). In general, CD28, CD69 and VLA-1 expression on BALF CD4+ lymphocytes and HLA-DR expression on BALF CD8+ lymphocytes was different in patients with hypersensitivity pneumonitis and sarcoidosis patients with parenchymal involvement. This BALF lymphocyte phenotype correlated with carbon monoxide diffusing lung capacity (Dlco) values across interstitial lung diseases (ILD) (r2 = 0.48, P = 0.0002). In sarcoidosis patients, CD8+CD28(null) blood lymphocytes correlated with lower Dlco values (r = -0.66, P = 0.004), chronic BALF lymphocyte activation phenotype (r2 = 0.65, P < 0.0001), radiographic staging (stage I versus stage II and higher, P = 0.006) and with the need for corticosteroid treatment (P = 0.001). Higher expression of CD69, VLA-1 and HLA-DR and lower expression of CD28 on BALF lymphocytes suggests prolonged stimulation and chronic lymphocyte activation in patients with ILD. In sarcoidosis, blood CD8+CD28(null) cells might be a new biomarker for disease severity but needs further investigation.

We present a case of a patient with pulmonary sarcoidosis who developed ulcerative sarcoidosis with granulomatous vasculitis on the lower legs. Ulceration is a rare presentation for sarcoidosis and this case gives further evidence that an underlying vasculitis may be an aetiological factor. Granulomatous vasculitis, classically associated with Wegener's granulomatosis, lymphomatoid granulomatosis, or Churg-Strauss syndrome, is also commonly described in pulmonary sarcoidosis. It has, however, only rarely been described in cutaneous sarcoidosis. Our patient's leg ulcers have responded well to immunosuppressive therapy with tapered corticosteroid and low-dose azathioprine.

Bullous pemphigoid has been reported to be induced or precipitated by systemic therapy with several drugs, including penicillamine, captopril, frusemide and ampicillin. We report an African male patient with sarcoidosis who was prescribed chloroquine for progressive dyspnoea. After 3 months he developed generalized pruritus which evolved into a widespread bullous eruption with acral targetoid lesions resembling erythema multiforme. The histological and immunofluorescence findings were diagnostic of bullous pemphigoid. The atypical clinical features of this case resemble the phenotype that has been noted in previous reports of drug-induced bullous pemphigoid.

Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology. The condition commonly affects young adults and frequently presents with bilateral hilar lymphadenopathy with or without pulmonary infiltration, ocular or cutaneous lesions. The clinical presentation can be extremely varied depending upon the organs affected. The diagnosis is firmly established when recognised clinical and radiographic findings are supported by histological evidence of discrete non-necrotising epithelioid cell granulomata in one or more organs. Sarcoidosis is usually self-limiting with spontaneous resolution, although in a few patients there is a progressive downhill course, culminating in irreversible fibrosis and severe impairment of organ function.

We present a patient with muscle manifestations of sarcoidosis associated with raised creatine kinase levels, eosinophilia and interstitial lung disease. She had significant improvement on prednisolone 30 mg per day.