Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25–50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren’s syndrome, lupus pernio, Heerfordt’s syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.

Sarcoidosis is an inflammatory disease that involves the eyes in 10–55% of cases, sometimes without systemic involvement. All eye structures can be affected, but uveitis is the most common ocular manifestation and causes vision loss. The typical ophthalmological appearance of these uveitis is granulomatous (in cases with anterior involvement), which are usually bilateral and with synechiae. Posterior involvement includes vitritis, vasculitis and choroidal lesions. Tuberculosis is a classic differential diagnosis to be wary of, especially in people who have spent time in endemic areas. The diagnosis is based on histology with the presence of non-caseating epithelioid granulomas. However, due to the technical difficulty and yield of biopsies, the diagnosis of ocular sarcoidosis is often based on clinico-radiological features. The international criteria for the diagnosis of ocular sarcoidosis have recently been revised. Corticosteroids remain the first-line treatment for sarcoidosis, but up to 30% of patients require high doses, justifying the use of corticosteroid-sparing treatments. In these cases, immunosuppressive treatments such as methotrexate may be introduced. More recent biotherapies such as anti-TNF are also very effective (as they are in other non-infectious uveitis etiologies).

Distinguishing between macrophage activation syndrome (MAS) and a simple flare of Still’s disease (SD) may be challenging. We sought to clarify the clinical features and outcome of MAS in SD and to explore predictive factors of MAS development. Demographic and clinical data, treatments, and outcomes were recorded in a cohort of 206 SD patients. SD patients with and without MAS were compared. To explore predictive factors for the development of MAS, patients were compared at the time of SD diagnosis. Twenty (9.7%) patients experienced MAS, which was inaugural in 12 cases. Patients with MAS were more likely to have hepatomegaly (OR, 3.71; 95% CI, 1.14–11.2; p = 0.03) and neurological symptoms (OR, 4.43; 95% CI, 1.08–15.3; p = 0.04) than patients without MAS. Cytopenias, abnormal liver tests, and coagulation disorders were significantly more frequent in patients with MAS; lactate dehydrogenase and serum ferritin levels were significantly higher. An optimized threshold of 3500 μg/L for serum ferritin yielded a sensitivity (Se) of 85% and a negative predictive value (NPV) of 97% for identifying patients with/without MAS. Survival analysis showed that a high ferritin level at the time of SD diagnosis was predictive of MAS development (p < 0.001). Specific factors, including neurological symptoms, cytopenias, elevated LDH, and coagulopathy, may contribute to the early detection of MAS. Extreme hyperferritinemia at the onset of SD is a prognostic factor for the development of MAS.

Spondyloarthritis (Spa), Behçet’s disease (BD) and sarcoidosis are major systemic inflammatory diseases worldwide. They are all multisystem pathologies and share a possible ocular involvement, especially uveitis. We hereby describe selected cases who were referred by ophthalmologists to our internal medicine department for unexplained uveitis. Physical examination and/or the use of laboratory and imaging investigations allowed to make a diagnosis of a systemic inflammatory disease in a large proportion of patients. In our tertiary referral center, 75 patients have been diagnosed with Spa (n = 20), BD (n = 9), or sarcoidosis (n = 46) in the last two years. There was a significant delay in the diagnosis of Spa-associated uveitis. Screening strategies using Human Leukocyte Antigen (HLA)-B27 determination and sacroiliac magnetic resonance imaging in patients suffering from chronic low back pain and/or psoriasis helped in the diagnosis. BD’s uveitis affects young people from both sexes and all origins and usually presents with panuveitis and retinal vasculitis. The high proportion of sarcoidosis in our population is explained by the use of chest computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography CT that helped to identify smaller hilar or mediastinal involvement and allowed to further investigate those patients, especially in the elderly. Our results confirm how in these sight- and potentially life-threatening diseases a prompt diagnosis is mandatory and benefits from a multidisciplinary approach.

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.

Sarcoidosis is a systemic granulomatous disease of unknown cause characterized by a wide variety of presentations. Its diagnosis is based on three major criteria: a clinical presentation compatible with sarcoidosis, the presence of non-necrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. Many conditions may mimic a sarcoid-like granulomatous reaction. These conditions include infections, neoplasms, immunodeficiencies, and drug-induced diseases. Moreover, patients with sarcoidosis are at risk of developing opportunistic infections or lymphoma. Reliably confirming the diagnosis of sarcoidosis and better identifying new events are major clinical problems in daily practice. To address such issues, we present seven emblematic cases, seen in our department, over a ten-year period along with a literature review about case reports of conditions misdiagnosed as sarcoidosis.