Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis

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.

Löfgren’s Syndrome

Löfgren’s syndrome presents as acute sarcoid arthritis, with a triad of hilar adenopathy, acute polyarthritis and erythema nodosum. Löfgren’s syndrome is self-limited, erythema nodosum, hilar adenopathy and acute polyarthritis usually resolve within a few weeks to months, however polyarthritis can last for up to 2 years. Treatment involves symptomatic control with NSAIDs/colchicine or oral glucocorticoids until symptoms resolve, if disease is resistant to these therapies, hydroxychloroquine, methotrexate or infliximab can be used. Löfgren’s syndrome is a rare presentation of sarcoidosis occurring in only about 5–10% of sarcoid patients. It is, however, important to recognize as it is the most common form of acute sarcoid arthritis and prompt treatment can prevent unnecessary prolonged discomfort for patients.

ANCA-negative microscopic polyangiitis with diffuse alveolar hemorrhage masquerading as congestive heart failure

Background Microscopic polyangiitis (MPA) is a subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), involving small and medium sized vessels, often affecting the kidneys and lungs. Anti-neutrophil cytoplasmic antibody (ANCA) is detected in up to 90% of cases of MPA and its detection helps guide diagnosis, however cases of ANCA-negative MPA have been reported, hence definitive diagnosis relies on tissue biopsy. Case report A 23-year-old man was evaluated for dyspnea and pleuritic chest pain, and found to have bilateral intra-alveolar opacities and hilar adenopathy. Diagnostic work up revealed positive anti-nuclear antibodies (ANA) and negative ANCA, which in the setting of a non-classical presentation, delayed diagnosis and appropriate treatment. Due to persistent symptoms and a high suspicion for autoimmune disease with pulmonary-renal syndrome, he underwent lung biopsy which revealed intra-alveolar hemorrhage and capillaritis indicative of microscopic polyangiitis (MPA). Surprisingly, kidney biopsy was not typical of classic MPA, but revealed less common features. Due to therapeutic noncompliance he was readmitted multiple times thereafter with rare complications of MPA such as acute pancreatitis and hemorrhagic pericardial effusion with tamponade. Conclusion This case serves as an important clinical reminder to consider AAV even in those with negative ANCA serologies and a high suspicion for pulmonary-renal syndrome. It also demonstrates the high morbidity in cases of diagnostic delay and inadequate treatment.

A Coronavirus Disease 2019 (COVID-19) Mystery: Persistent Fevers and Leukocytosis in a Patient With Severe COVID-19

Short-course glucocorticosteroids are being used and tocilizumab (TCZ) had been used to treat patients with severe coronavirus disease 2019 (COVID-19) disease. These agents, when administered individually, have been associated with tuberculosis (TB) during chronic use. We report a case of TB in a 44-year-old male with diabetes and severe COVID-19 who received high-dose short-course glucocorticosteroids and a single dose of TCZ. The clinical presentation was atypical with unresolving fevers and leukocytosis, progressive lower lobe cavities, and hilar adenopathy. Delayed diagnosis led to prolonged hospitalization and extensive antibiotic use.

P1310 Prosthetic valve endocarditis or thrombus?

One cause of constitutional syndrome in patients previously submitted to valve replacement surgery is a prosthetic endocarditis; this occurs in 1-6% of valve surgeries and has an adverse prognosis. Although this is a likely etiology, it is important to keep other possibilities in mind. This clinical case is about a 61 years old male, with known history of smoking, atrial fibrillation anticoagulated with warfarin (with low TTR), and rheumatic fever in childhood, with severe aortic stenosis/regurgitation and moderate mitral regurgitation. In August 2018 he was admitted in our hospital with mitral valve endocarditis cause by Streptococcus agalactiae. He was submitted to an aortic and mitral valve replacement surgery with 2 bioprothesis. Three months later he was admitted again with weight loss, fatigue, dyspnea for small efforts and worsening anemia. The first diagnosis hypothesis was prosthetic endocarditis. The echocardiogram showed normo-functioning aortic bioprothesis; obstructive mitral bioprothesis with an image suggestive of a vegetation; and a de novo mass in the left auricle, compatible with a thrombus. This clinical case was discussed in Heart Team: as the patient was clinically stable, it was opted for an initial conservative approach; although there was a strong clinical suspicion that all the clinical case was due to thrombotic manifestations (assuming that the vegetations had a non-infectious origin), he was nonetheless medicated with vancomycin, gentamicin and rifampicin, as the diagnosis of early culture negative prosthetic endocarditis could not be discarded. He was anticoagulated with enoxaparin. In the reevaluation echocardiogram there was a significative reduction of the left atrial thrombus and disappearance of the mitral valve vegetation image, with improvement of the mitral valve prosthetic gradients. The case was discussed again in Heart Team: due to the clinical evolution, the hypothesis that this was all caused by a thrombotic manifestation grew stronger; it was opted not to submit the patient to a new surgery and the antibiotic therapy was suspended. To study the pro-thrombotic state and the constitutional syndrome, a full body CT was requested: "hilar-mediastinal and bilateral hilar adenopathy; right supraclavicular adenopathy; splenomegaly with infarcted area." The right hilar adenopathy was biopsied; the pathologic exam revealed non-small cells lung carcinoma. The patient was discharged, medicated with warfarin and oriented to outpatient Oncology consult. Any cancer can be associated with thrombotic manifestations. In this case, considering the heavy smoking burden, lung cancer is one of the first etiologies to consider. The thrombotic manifestations of the non-small cells lung carcinoma are due to a paraneoplastic mechanism and might precede the cancer diagnosis. This clinical case highlights the importance of thinking of different etiologies in the differential diagnosis of a constitutional syndrome. Abstract P1310 Figure. Left auricle mass

Distribution and Characteristics of Intrathoracic Lymphadenopathy in TB/HIV Co-Infection

Background: Intrathoracic Lymphadenopathy (ITLN) in Human Immunodeficiency Virus (HIV) infected patients may have various etiologies and prognoses. Etiologies of ITLN can be distinguished based on the distribution of enlarged lymph nodes. Sometimes tuberculosis (TB) is the first sign of underlying HIV infection. Objective: We sought to determine ITLN distribution and associated pulmonary findings in TB/HIV co-infection using Computed Tomography (CT) scan. Methods: In this retrospective, observational, cross-sectional study, chest CT scans of 52 patients with TB/HIV co-infection were assessed for enlarged intrathoracic lymph nodes (>10 mm in short axis diameter), lymphadenopathy (LAP) distribution, calcification, conglomeration, the presence of hypodense center and associated pulmonary abnormalities. LAP distribution was compared in TB/HIV co-infection with isolated TB infection. Results: Mediastinal and/or hilar LAP were seen in 53.8% of TB/HIV co-infection patients. In all cases, LAP was multinational. The most frequent stations were right lower paratracheal and subcarinal stations. Lymph node conglomeration, hypodense center and calcification were noted in 25%, 21.4% and 3.5% of patients, respectively. LAP distribution was the same as that in patients with isolated TB infection except for the right hilar, right upper paratracheal and prevascular stations. All patients with mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Conclusion: All patients with TB/HIV co-infection and mediastinal and/or hilar adenopathy had associated pulmonary abnormalities. Superior mediastinal lymph nodes were less commonly affected in TB/HIV co-infection than isolated TB.

The Results of a Three Year Analysis on Sarcoidosis Patients Registered in the Regis Electronic Registry

Introduction. Registries are necessary particularly for rare diseases. The REGIS registry was developed to improve scientific research in the field of interstitial lung diseases (ILDs).Material and Method. We analysed 144 patients with interstitial lung diseases enrolled during a three year period, selected the sarcoidosis cases and analysed the data with Excel 2007 Software.Results. A number of 26 sarcoidosis patients were included (18.06% out of the total), of which 46.15% were female, with an average age of 41.34±9.84 years; 23.08% were smokers. 88.46% pf patients had mediastinum pulmonary involvement: stage II in 17 patients, stage III in 5 patients and stage IV in one patient; only 3 patients had extra thoracic involvement. The medical investigations performed were: chest X-ray (96.15%), thoracic HRCT (96.15%) that identified hilar adenopathy (96%), nodules (68%), with peribronchovascular localization (44%); spirometry (96.15%) that revealed an average CV of 94.99±23.07% out of the predicted value, DLCO 78.41±19.39% out of the predicted value; bronchoalveolar lavage (38.46%); serum angiotensin-converting enzyme (73.08%) and pulmonary or lymph node biopsy (80.77%). The patients that needed treatment (46.15%) were administered oral corticosteroids (10 patients), acetylcysteine (1 patient) and pirfenidone (1 patient).Conclusions. The number of patients enrolled is low as a result of the voluntary reporting, especially in severe cases and with access to all investigations needed for diagnosing.

Mycoplasma Pneumonia: An Unrecognized Cause of Fever of Unknown Origin in an Adult

A 26-year-old female was admitted for fever of unknown origin (FUO), headaches, left ankle edema, and a lower extremity rash consistent with erythema nodosum. She had no respiratory symptoms or family history of autoimmune diseases. A chest X-ray was negative for pneumonia or hilar adenopathy. Extensive autoimmune workup was negative. A chest, abdomen, and pelvis computed tomography scan was unremarkable and laboratory studies revealed no source of infection. On hospital day 5, the patient developed a mild productive cough. Her Mycoplasma pneumonia (MP) IgM was high, confirming the diagnosis of MP induced FUO. She was started on azithromycin 500 mg daily and within 24 hours her fevers and headaches resolved. Her left ankle edema and EN gradually improved over a course of a few weeks. This case report highlights the need for MP testing in the evaluation of fever of unknown origin, even in the absence of pulmonary manifestations.

Diagnostic yield of transbronchial needle aspiration for lymphoma

<p>Background. Transbronchial needle aspiration (TBNA) is a minimally invasive bronchoscopic technique that is cost-effective and safe for diagnosing mediastinal and hilar adenopathy in lung cancer, other malignancies, sarcoidosis and infectious processes such as tuberculosis. Few studies have analysed the sensitivity, specificity and predictive values of TBNA for diagnosing lymphoma.</p><p>Objective. To evaluate the diagnostic yield of TBNA for diagnosing mediastinal and hilar adenopathy in suspected lymphoma.</p><p>Methods. We performed a retrospective analysis of collected data of patients with mediastinal and hilar adenopathy adjacent to the tracheobronchial tree detected by thoracic computed tomography, who underwent TBNA at Tygerberg Hospital between July 2010 and June 2013. We included 25 patients with suspected or proven lymphoma. Histology was used as the gold standard.</p><p>Results. Adequate samples for cytological evaluation were obtained for 22 (88%) patients. Cytological diagnosis was possible for 8 (32%). For 17 (68%) who could not be diagnosed by TBNA alone, histology provided final diagnosis. Rapid on-site examination (ROSE) was performed in 23 (92%). In 17/23 (74%) cases, these had similar results to formal cytology. Only 4 (16%) had flow cytometry requested. Twelve (48%) had lymphoma confirmed on histology. TBNA cytology had 100% specificity and positive predictive value for suspicion of lymphoma. Sensitivity was 33% and negative predictive value 62%.</p><p>Conclusion. TBNA is an appropriate first-line diagnostic procedure in evaluating mediastinal and hilar lymphadenopathy in suspected lymphoma. Biopsy should be the immediate second-line procedure when ROSE/cytology is suspicious of lymphoma or shows atypical cells. Patients with negative TBNA cytology, but high clinical or radiological suspicion of lymphoma, should be further investigated.</p>