Hidenobu Shigemitsu

Multinational evidence-based World Association of Sarcoidosis and Other Granulomatous Disorders recommendations for the use of methotrexate in sarcoidosis: integrating systematic literature research and expert opinion of sarcoidologists worldwide.

Purpose of review Although glucocorticosteroids are considered the first-line treatment in sarcoidosis, refractory cases require alternatives, such as methotrexate (MTX). The aim of this study was to develop, on behalf of the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG), multinational evidence-based recommendations for the use of MTX in sarcoidosis for routine clinical practice. Recent findings A systematic literature search was conducted and combined with the opinions of sarcoidosis experts worldwide to formulate the recommendations. An online survey concerning 10 clinical questions was sent through the WASOG newsletter to sarcoidosis experts. Agreement about the recommendations amongst the worlds leading sarcoidologists was evaluated. A total of 237 articles were identified, 43 of which were included. Randomized controlled trial evidence supporting the use of MTX in sarcoidosis was limited. Forty-five per cent (113 of 250) of the sarcoidosis experts contacted completed the survey (Europe 55%, North America 26% and Asia 12%). Ten recommendations were formulated concerning the indications for use, starting dose, folic acid, work-up, contraindications, monitoring, administration options in case of adverse gastrointestinal effects, hepatotoxicity, long-term safety and use during pregnancy and breast feeding. Summary Ten multinational evidence-based recommendations for the use of MTX in sarcoidosis were developed, which are supported by the worlds foremost sarcoidosis experts.

IgG4-related interstitial lung disease: a new and evolving concept

Purpose of review This review examines recent advances in our knowledge of the clinical, pathological, diagnostic, and therapeutic aspects of IgG4-related interstitial lung disease (ILD). Recent findings A recent case series of ILD with IgG4-positive plasma cells suggested grade 1 lymphomatoid granulomatosis. The presence of the IgG4-positive plasma cells with the lack of atypical cells favored IgG4-related ILD as a diagnosis. In another case study, four out of 30 patients with autoimmune pancreatitis developed pulmonary involvement during follow-up. Elevations of IgG4 and Krebs von den Lungen-6 levels were associated and thought to be predictive of the development of IgG4-related lung disease. A retrospective analysis investigating radiological/pathologic correlation in IgG4 lung disease identified computed tomographic features pathologically corresponding to IgG4-related sclerosing inflammation in the pulmonary interstitium. Summary IgG4-related ILD is a new and evolving entity. It can occur with or without systemic involvement. Larger studies are necessary to elucidate the exact mechanism and clinical characteristics of this disorder.

Gastric Sarcoidosis and Review of the Literature

Sarcoidosis is a systemic disease with a 90% predilection for the lungs, but any organ can be involved. Gastrointestinal involvement is rare. Within the gastrointestinal system, gastric involvement is the most common. When this organ system is involved, it can be a feature of systemic disease or an isolated case. Gastrointestinal sarcoid can resemble a broad spectrum of other disease processes; thus, it is important for health care providers to be familiar with the various gastrointestinal manifestations. Patients can have subclinical symptoms or have symptoms of epigastric pain, nausea, vomiting, and hematemesis. We present 2 cases of gastric sarcoid and a MEDLINE search of 44 reported cases of gastric sarcoid based on a compatible history and the demonstration of noncaseating granulomas. We describe the clinical manifestations of symptomatic gastric sarcoid in relation to the endoscopic findings.

Pulmonary hypertension and granulomatous vasculitis in sarcoidosis

Purpose of review To examine the recent advancements of the epidemiology, pathophysiology, clinical characteristics, radiographic studies, diagnostic modalities, treatment, and prognosis of pulmonary hypertension in sarcoidosis. Recent findings A large retrospective study found 73.8% of patients with sarcoidosis listed for transplant had pulmonary hypertension. Several other studies found pulmonary hypertension to be associated mostly with advanced sarcoidosis, although frequencies in nonfibrotic disease were not uncommon. Destruction of vasculature due to fibrotic lung disease is most likely the common cause; however, other mechanisms have been proposed. In a small study, pulmonary venous occlusive disease was observed in the explanted lungs. Several studies have found an association with pulmonary function and the incidence of pulmonary hypertension. Right heart failure was seen in 21–23% of patients. In one study, high-resolution computer tomography findings, such as presence of lymphadenopathy, opacities, and thickened bronchovascular bundles, were not significantly different. Septal lines and ground-glass opacities were found at higher frequency in sarcoidosis-associated pulmonary hypertension. Corticosteroids were effective in treating some patients with sarcoidosis-associated pulmonary hypertension. Inhaled nitric oxide, epoprostenol, and bosentan have been shown to be efficacious in a small number of patients. Summary Pulmonary hypertension is not infrequently observed in sarcoidosis. Further studies are needed to elucidate the epidemiology, mechanisms, treatment, and significance of sarcoidosis-associated pulmonary hypertension.

Chronic interstitial pneumonitis in end-stage sarcoidosis

To the Editors: End-stage sarcoidosis is typically characterised by severe interstitial fibrosis occurring along the bronchovascular bundles with cystic changes 1, 2. Chronic interstitial pneumonitis typically occurs in the early stages of sarcoidosis and is localised to the areas affected by granulomas 3–5. Herein, we report end-stage sarcoidosis patients who underwent lung transplantation at our centre (University of Southern California, Keck School of Medicine, Los Angeles, CA, USA) and who surprisingly had evidence of moderate-to-severe chronic interstitial pneumonitis, which was previously considered atypical in end-stage sarcoidosis. Furthermore, two patients had a pattern resembling usual interstitial pneumonitis (UIP) with fibroblastic foci. We reviewed the charts and microscopic slides of all sarcoidosis patients who underwent lung transplantation at the University of Southern California. Patients were only included if the initial biopsy reports used to support the diagnosis contained descriptions compatible with a diagnosis of sarcoidosis and/or met the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders criteria 6. All microscopic slides from the explanted lungs and mediastinal/hilar regional lymph nodes from these patients were examined by two pathologists (J.M. Oblad and M.N. Koss) who were unaware of any clinical information except for the history of lung transplantation for sarcoidosis. The pathologists were asked to grade the average granuloma burden (lung and lymph nodes) and interstitial fibrosis (lung) individually as follows. Grade 0 (absent): no granulomas or fibrosis detected in the specimen; Grade 1 (mild): less than two granuloma per low-power field (lpf) or occasional foci of fibrosis per low lpf; Grade 2 (moderate): two to five granuloma per lpf or <50% of parenchyma with …

Is sarcoidosis frequent in patients with cancer

Purpose of review To examine the recent advancements of the epidemiology, pathophysiology, and clinical characteristics in patients who have a history of sarcoidosis and cancer. Recent findings A longitudinal study examined 1153 patients with sarcoidosis utilizing the computerized healthcare dataset available in the United Kingdom. The authors found increased incidence of cancer in patients with sarcoidosis mainly due to skin cancer (rate ratio 1.86; 95% confidence interval 1.11–3.11). Endobronchial ultrasound guided transbronchial needle aspiration for mediastinal adenopathy in patients found 11% (17 out of 153) of patients to have noncaseating granulomas. Of the 17 patients, eight had sarcoid-like lymphadenopathy, another eight had sarcoidosis, and one had nontuberculous mycobacterial infection. Another study examined the presence of granulomas in patients with testicular carcinoma, which showed either sarcoid-like reaction or sarcoidosis. Eighty percent of patients with granulomas regressed spontaneously and did not appear to affect the prognosis of cancer. Conclusion Is there a causal or accidental relationship between sarcoidosis and cancer? We do not know. However, we would like to propose the term ‘sarcoid-cancer syndrome’ that would encompass sarcoid-like reaction and multisystem sarcoidosis occurring in patients with cancer and various lymphomas. Further studies are needed to elucidate the precise mechanism and epidemiology, clinical features, and pathogenesis of this phenomenon.

Aspiration pneumonias: under-diagnosed and under-treated.

Purpose of review To examine recent advancements of the epidemiology, risk factors, bacteriology, diagnostic measures, and treatment for aspiration pneumonia. Recent findings In a large prospective study, 10.3% of community-acquired pneumonia requiring hospitalization was associated with aspiration pneumonia, as opposed to 30% when patients were admitted from long-term facilities. A murine stroke model showed increased apoptosis of cell-mediated immune cells due to overactivation of the sympathetic nervous system. Subsequent nasal inoculum of low-dose Streptococcus pneumoniae caused severe pneumonia. Another murine study showed intratracheal administration of hydrochloric acid-primed lungs more susceptible to infection with Klebsiella pneumoniae. Tracheal pH monitoring demonstrated acidification of trachea in 28% of patients with acute stroke deemed to be safe for oral feeding. Various antimicrobial agents used to treat aspiration pneumonia have comparable success rates. However, clindamycin was the only agent that did not propagate emergence of methicillin-resistant Staphylococcus aureus. Summary Aspiration pneumonia is prevalent in community-acquired pneumonia. Further studies are needed to elucidate the effects of sympathetic nervous system and aspiration pneumonitis as primers for lung infection. Predicting aspiration risk is difficult and newer diagnostic tools are necessary. Antimicrobials used in aspiration pneumonia have similar success rates although the development of resistant organisms must be monitored.

Sarcoidosis and interstitial pulmonary fibrosis; two distinct disorders or two ends of the same spectrum.

Purpose of review Pulmonary fibrosis is a reparative response characterized by accumulation of extracellular matrix in the lung parenchyma that may be observed in end-stage sarcoidosis. This article will discuss the recent advancements in the understanding of the pathogenesis of pulmonary fibrosis in sarcoidosis in comparison with idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP). Recent findings A recent study examined clinical, radiographic, and histopathologic findings of end-stage sarcoidosis patients with lung fibrosis who underwent lung transplantation. The authors found many of the patients to have moderate-to-severe interstitial pneumonitis in some cases with UIP considered to be atypical of end-stage sarcoidosis. Furthermore, these patients had diagnosis of sarcoidosis for a shorter time prior to transplant compared with individuals without interstitial pneumonitis (mean 4.8 years vs. 23.3 years). Another study found a promoter polymorphism in prostaglandin-endoperoxide synthase 2 (PTGS2), −765G>C, to be associated with susceptibility and increased risk for pulmonary fibrosis in sarcoidosis in the white population compared with healthy controls. An altered Sp1/Sp3 binding to the −765 region has been proposed as a possible mechanism for reduced PTGS2 expression. Summary A subset of patients with sarcoidosis that progresses to pulmonary fibrosis may share some similar mechanistic and morphologic aberrations with IPF/UIP. Future studies are needed to examine the significance of chronic interstitial pneumonitits and UIP pattern in fibrotic sarcoidosis as a potential marker for progressive disease, and the roles of PTGS2 polymorphism in various ethnic groups and Sp1/Sp3 binding in other fibrotic lung diseases.

A 65-Year-Old Woman With Subcutaneous Nodule and Hilar Adenopathy

A 6,5-year-old woman presented with an elongated, painless soft-tissue swelling involving the ulnar aspect of the right forearm and a few erythematous, nontender, and nonpruritic papules on both thighs and trunk. She denied any fever, chills, or night sweats. Her history was significant only for asthma and hypothyroidism. On evaluation, the mass was firm but mobile with no discoloration of the overlying skin (Fig 1). There were no associated motor or sensory impairments and no history of trauma. The rest of the history and physical examination were noncontributory. MRI of the right forearm revealed an elongated mass extending approximately 14 em along the ulnar aspect of the forearm. The mass had low signal intensity similar to muscle on the T1-weighted image shown below (Fig 2) and high signal intensity on the T2-weighted image. The lesion was enhanced with gadolinium (Fig 3). The mass was removed, and the biopsy specimens showed noncaseating granulomas without acid-fast bacilli, fungi, other organisms, or foreign-body particles. A chest radiograph revealed bilateral hilar adenopathy (Fig 4).

A Middle-Aged Man With Cough, Chest Pain, and Pulmonary Artery Filling Defect

A middle-aged man with no past medical history presented to the ED after 2 weeks of productive cough, rhinorrhea, high-grade fevers, and chills. He had been treated with ibuprofen, promethazine cough syrup, and albuterol as an outpatient without any relief. He had associated dull, nonradiating anterior chest wall pain and unintentional weight loss of 10 lb during the course of his illness. On evaluation, he was noted to speak in short sentences of four to fi ve words with labored breathing.