Complete atrioventricular block with a 22-month history of ocular sarcoidosis: a case report

A 52-year-old woman with acute uveitis associated with ocular sarcoidosis developed complete atrioventricular block 22 months after the initial diagnosis was made. Cardiac sarcoidosis is a serious and, not infrequently, a fatal disease. Although it is difficult to establish the clinical diagnosis of cardiac sarcoidosis, a serial ECG is considered necessary in patients with any kind of sarcoidosis.     

Variation in immunoglobulin levels and circulating immune complexes in sarcoidosis. Correlation with extent of disease and duration of symptoms

Sixty-three patients with clinically definite sarcoidosis confirmed histologically and/or by a positive Kveim test were studied according to the clinical and radiographic extent and known duration of their disease and symptoms. Immunoglobulin levels were not raised among patients with bilateral hilar lymphadenopathy (BHL) alone, but IgG and IgA were raised among patients with pulmonary sarcoidosis, most markedly among patients with long-standing active disease. Serum IgM was found elevated in extrathoracic sarcoidosis. West Indian males had the highest levels of IgG. The presence of circulating immune complexes reacting with conglutinin was strongly associated with a recent symptomatic onset of sarcoidosis; they were more prevalent in patients with BHL and erythema nodosum. In contrast, polyethylene glycol precipitable immunoglobulins were associated with long-standing active disease and with neurologic involvement.     

A case of primary pulmonary cavitation with thin smooth walls in sarcoidosis]

A 27-year-old female was admitted to our hospital after a regular medical check revealed BHL and cavitation in the right upper lung field on a chest radiograph. Ga scintigraphy showed abnormal uptake bilaterally in the mediastinal and hilar lymph nodes. We strongly suspected lung sarcoidosis, then performed TBLB and BAL. BAL fluid disclosed a high proportion of lymphocytes with a marked elevation of the CD4/CD8 ratio, compatible with sarcoidosis. A TBLB specimen revealed non-caseating epithelioid cell granuloma compatible with a diagnosis of lung sarcoidosis. From the clinical and radiological observations, it was concluded that the cavitation in the present case was primary pulmonary cavitation in sarcoidosis, as distinct from infection, malignancy, bulla or cystic bronchiectasis. Chest radiographs taken a half year after diagnosis showed reduction of the cavitary lesion and disappearance of BHL.     

Crohn's disease mimicking sarcoidosis in bronchoalveolar lavage.

Granulomatous disorders like sarcoidosis or Crohn's disease are commonly associated with extrapulmonary or extraintestinal manifestations which occasionally may represent the only symptoms. We describe a 28-year-old female patient suffering from atypical erythema nodosum and arthritis. Although the chest x-ray was unremarkable bronchoalveolar lavage revealed lymphocytic alveolitis with an elevated CD4/CD8 ratio of 8 and 11.4 at repeated examinations suggesting a diagnosis of sarcoidosis. Further diagnostic workup included endoscopy of the bowel. The macroscopic aspect and histology of the terminal small bowel and colon ascendens indicated Crohn's disease. The patient recovered on steroids and sulfasalazine. Six months later she developed a perianal abscess for which she needed surgery supporting the diagnosis of Crohn's disease. This is the first case of a significantly (>6) elevated CD4/CD8 ratio in Crohn's disease previously regarded as highly specific for sarcoidosis.     

Sarcoidosis with primary acute cavitation exacerbated by bronchial asthma]

A 22-year-old woman complaining of blurred vision visited our hospital in March 1995 and was given a diagnosis of uveitis. Chest X-ray and computed tomographic (CT) films demonstrated bilateral hilar lymphadenopathy (BHL), diffuse granular shadows in both lung fields, and a cavity with a thin, smooth wall in the right upper lung field. Because histopathologic findings from transbronchial lung biopsy specimens of the lung and cavity tissues disclosed sarcoid granuloma, the diagnosis was sarcoidosis with primary cavitation, which is very rare for this disease. Although BHL disappeared without medication, in November the patient experienced dyspnea due to attacks of bronchial asthma that had been in remission for a long period. Treatment with inhalation of becromethazone propionate markedly alleviated her symptoms. In May 1998, follow-up chest CT films demonstrated that the cavity had disappeared. This case suggested that sarcoidosis leads to a deterioration of asthma control, a conclusion supported by previous reports.     

Coeliac disease associated with sarcoidosis and antiphospholipid syndrome: A case report

Background

Sarcoidosis is a clinically heterogenous disease of unknown etiology with a hallmark of the development and accumulation of non-caseating granulomas in any organ. The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by an elevated risk for arterial and venous thrombosis and pregnancy-related morbidity. Celiac disease (CD) is a chronic, immune-mediated form of enteropathy that is now presenting later in life and often with extraintestinal manifestations. Co-existence of sarcoidosis, CD and APS is extremely rare.

Sarcoidosis with acute recurrent polyarthritis and hypercalcemia

A 45-year-old woman had bleary eyes and recurrent episodes of fever and arthritis in the knees and ankles. The patient had anterior uveitis, negative findings of the tuberculin test, and an increased serum lysozyme level, but bilateral hilar lymphadenopathy (BHL) was absent. During the course of her disease, the serum calcium and angiotensin-converting enzyme levels gradually increased to above the normal level, and the patient was clinically diagnosed as having sarcoidosis. The clinical features of arthritis were typical of those of L?fgrens syndrome although BHL and erythema nodosum were absent. The patient was successfully treated with 15 mg/day of prednisolone.     

Diagnosis and parameters for the evaluation of disease activity and prognosis in patients with pulmonary sarcoidosis

We evaluated the usefulness of serum ACE, BALF lymphocyte%, CD4+/CD8+ ratio when diagnosing pulmonary parenchymal lesion in patients with sarcoidosis. The results showed the substantial usefulness but lesser specificity. Furthermore, we evaluated the values of the above three parameters in terms of the judgment of the disease activity and the reliability for foreseeing the prognosis in BHL sarcoidosis. Elevated serum ACH had a good relationship with the disease activity in both nonsmoker and smoker cases. BALF lymphocyte % also had in smoker cases. But none of three parameters showed a significant relationship with the prognosis in BHL sarcoidosis.     

Alveolar Lymphocytosis in Patients with Chronic Uveitis: Relationship to Sarcoidosis

Bronchoalveolar lavage (BAL) is frequently performed in patients with suspected ocular sarcoidosis. This study describes the immunogenetical, immunological, radiological, and functional features of a subclinical alveolar lymphocytosis unrelated to sarcoidosis in patients with chronic uveitis. Two hundred and ten patients with chronic uveitis of unknown origin, who underwent fiber-optic bronchoscopy with BAL as part of a prospective protocol over a three-year period, were evaluable for retrospective analysis. Sixty-five patients had alveolar lymphocytosis: Sarcoidosis was diagnosed in 13 (6%) patients, whereas alveolar lymphocytosis was considered unrelated to sarcoidosis in 52 (25%). Alveolar lymphocytosis unrelated to sarcoidosis was not associated with radiologically detectable interstitial lung disease or pulmonary function impairment. CD4/CD8 lymphocyte ratio was 3.7 +/- 3.0. Total cell count, total lymphocyte, and CD4 lymphocyte percentage were significantly lower when compared with sarcoidosis-related alveolitis (129,000 +/- 80,000 vs. 218,000 +/- 117,000, p <0.05; 33.1% +/- 13.2 vs. 39.7% +/- 13.2, p <0.05; and 54.3% +/- 18.2 vs. 65.4% +/- 10.1, p <0.05, respectively). Patients with alveolar lymphocytosis unrelated to sarcoidosis were older (47.8 +/- 17.7 years vs. 42.7 +/- 14.2 years, p <0.05) and more likely to carry the HLA-B51 allele (19.7% vs. 7.1%, p <0.01) than patients with chronic uveitis without alveolar lymphocytosis. They did not appear to be at risk of developing clinically apparent interstitial lung disease on followup. We conclude that alveolar lymphocytosis is frequently observed in patients with chronic uveitis. It is generally unrelated to sarcoidosis and may then be associated with a distinctive immunogenetic phenotype.     

Propionibacterium acnes-associated Sarcoidosis Possibly Initially Triggered by Interferon-alpha Therapy

A 46-year-old woman with uveitis was referred to our respiratory diseases department in July 2018. Her medical history included transient bilateral hilar mediastinal lymphadenopathy (BHL) and multiple pulmonary nodules in May 2013 during pegylated interferon-alpha and ribavirin treatment for chronic hepatitis C infection. Five years post-treatment, chest X-ray revealed BHL and nodular recurrence. A biopsy of the subcutaneous buttock nodules revealed scattered non-caseating epithelioid granulomas with positive PAB immunohistochemical staining. This seem to be the first report of Propionibacterium acnes-associated sarcoidosis possibly initially triggered by interferon-alpha therapy. Understanding the mechanisms underlying interferon-triggered P. acnes-associated sarcoidosis may clarify the sarcoidosis immunopathogenesis.     

A case of sarcoidosis with primary acute pulmonary cavitation]

A 23-year-old man was admitted to our hospital on June 24, 1991, because of worsening chest X-ray findings of sarcoidosis. In August 1990, he was referred to our outpatient office, because of BHL and nodular lesions on chest X-ray film performed at his company 4 months earlier. At that time, serum ACE was elevated to 34.0 IU/l, and Ga scintigraphy showed abnormal uptake in bilateral lacrimal and salivary glands, mediastinal and hilar lymph nodes, and in the lung fields. TBLB specimen showed noncaseating epithelioid granuloma with giant cells and negative stains for acid-fast bacilli. Although it was planned to follow this patient without medication, he did not return to our outpatient department. In June 1991, because of worsening of lesions in the lung at annual checkup at his company, he was referred and admitted for steroid therapy. Chest X-ray film on admission showed BHL, multiple nodular lesions in both lung fields, and bullous change in the left upper lobe. Chest CT on admission showed three cavitating lesions within preexisting nodules. PPD skin test was negative, and sputum smears and cultures were repeatedly negative for pyogenic bacteria and acid-fast bacilli. Therapy was initiated with prednisolone 30 mg daily. Four months later, there was marked resolution of BHL and nodular lesions, and the cavitating lesions were no longer visible on chest X-ray film. From the clinical and radiological observations, it is concluded that the cavitating lesions in the present case were primary acute pulmonary cavitation in sarcoidosis, distinct from infection, bullae, or cystic bronchiectasis which are seen in the chronic and fibrotic stages of sarcoidosis.     

Acute-onset sarcoidosis with erythema nodosum and polyarthralgia (Löfgren's syndrome) in Japan: a case report and a review of the literature

L?fgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among white people, but is considered rare among Japanese people. We present the case of a 26-year-old Japanese woman with L?fgren's syndrome. The patient complained of polyarthritis and EN of the lower extremities that lasted for 3 months. A chest radiograph revealed BHL and nodular shadows. The angiotensin-converting enzyme (ACE) level was within the normal range. Transbronchial lung biopsy revealed a noncaseating granuloma with giant cells. Six Japanese cases of L?fgren's syndrome have been reported previously. Five of the seven Japanese patients with L?fgren's syndrome had normal ACE levels; all of them exhibited BHL. L?fgren's syndrome should be considered as a possibility when examining a patient with EN and articular symptoms, even if the patient is Japanese.     

Metastatic renal cell carcinoma simulating sarcoidosis. Analysis of 12 patients with bilateral hilar lymphadenopathy

Case summaries of four patients with bilateral hilar lymphadenopathy (BHL) caused by metastatic renal cell carcinoma are presented, and these and eight similar cases from the literature are analyzed. In nine patients, sarcoidosis was the provisional clinical diagnosis, but four of these patients had a past history of renal cell carcinoma. In the remaining five patients, a distinction from sarcoidosis could not be made by history, physical examination, and chest roentgenogram. This underscores the need for tissue confirmation in the diagnosis of sarcoidosis and alerts the physician to consider metastatic renal cell carcinoma in the differential diagnosis of BHL.     

结节病59例治疗及随访分析

目的探讨结节病的治疗、影响预后的因素及判断病情和预后的指标。方法回顾性分析1984年1月-2003年1月北京协和医院住院治疗且随访1〉2年的59例结节病临床资料。结果随访时间（61．9±49．4）个月。（1）0期患者7例,均在确诊后即口服糖皮质激素（以下简称激素）治疗,其中4例完全缓解。Ⅰ期患者22例,确诊后未予治疗的5例患者中1例进展,3例自愈,1例部分缓解;确诊后即予激素治疗的17例患者中,9例完全缓解,1例进展至Ⅱ期。Ⅱ期患者23例,1例在未予治疗3个月加重后及22例在确诊后开始激素治疗,13例完全缓解,2例进展至Ⅲ期。Ⅲ期5例患者均在确诊后即予激素治疗,1例治愈,2例进展至Ⅳ期。Ⅳ期患者2例,尽管长期激素治疗,病情仍在缓慢进展。（2）Ⅰ期、Ⅱ期患者发病时的支气管肺泡灌洗液（BALF）中细胞总数和分类、CD4／CD8比值及血清血管紧张素转换酶（sACE）水平差异无统计学意义。（3）共有24例患者复发,其中胸内结节病20例,14例有肺外受累;未复发者中10例有肺外受累;有肺外受累与无肺外受累比较,P=0．006。（4）完全缓解者发病时BALF中中性粒细胞数低于尚未缓解者（P〈0．001）。结论结节病病程有一定的自愈性。对Ⅰ期患者可先观察。有肺外病变的胸内结节病患者更易复发。发病时BALF中中性粒细胞数可能作为一个预测预后的指标。     

Ocular inflammatory disease in patients with polymyalgia rheumatica: A case series and review of the literature

Scleritis and uveitis are potentially blinding conditions that can be associated with systemic inflammatory diseases. Polymyalgia rheumatica (PMR) is a common rheumatic disorder of the elderly of uncertain etiology. Although there are a few published reports of scleritis and uveitis in PMR patients, the association of PMR to ocular inflammation has not been well established. The aim of this study is to report a series of PMR patients with scleritis and/or uveitis and review the prior published reports of this potential association. We retrospectively reviewed the medical charts of patients with PMR and scleritis or uveitis who were examined in the Ocular Immunology Service of Massachusetts Eye and Ear Infirmary. We also performed a systematic literature search (PubMed; January 1990 until January 2014) to identify earlier published reports. Seven PMR patients with ocular inflammatory disease (OID) were included in our study: two with scleritis, three with anterior uveitis, and two with panuveitis. The onset of PMR preceded the occurrence of OID in six patients, and in one patient uveitis developed 2 months prior to PMR. Five patients demonstrated a temporal association between flares of PMR and OID. In four patients, OID flares developed during tapering of systemic prednisone prescribed for PMR. Four of the five patients who had relapsing PMR had recurrent or persistent uveitis over the course of follow-up. PMR may be associated with both scleritis and uveitis and should be considered as a possible underlying cause of OID.     

An elderly case with sarcoidosis whose symptom of dementia was effectively treated by steroid

We report a case of a 74-year-old woman whose symptoms of dementia may have been caused by sarcoidosis and in whom steroid treatment was effective. The patient, who had recieved treatment for hypertension, started to exhibit symptoms of dementia one year previously and progressively deteriorated during the month before she was admitted. Brain computed tomography showed multiple lacunae infarctions. Chest X-ray showed mild swelling of bilateral lymph nodes in the mediastinum. The patient was referred to an ophthalmologist because of complaints of disturbed visual field, and bilateral uveitis was diagnosed. Negative tuberculin, high serum ACE value and high absorbance in the lung hila on Ga scintigram were recognized. Lymph node biopsy revealed typical granuloma compatible with sarcoidosis. Cerebrospinal fluid (CSF) showed elevated protein concentration without an increased cell count. EEG showed a diffuse slow wave pattern. We observed the progression of dementia shown by declining scores of Mini-Mental State Examination (MMSE) from 17/30 on admission to 7/30 on day 30 after admission. Although enhanced MRI of the brain showed no typical findings of sarcoidosis, we started treatment with prednisolone (50 mg/day) based on the suspicion that the progression of dementia was caused by sarcoidosis. One month after the start of steroid treatment, we observed gradual improvement of symptoms. The MMSE score increased to 20/30. According to previous reports, elderly sarcoidosis patients relatively rare by show dementia, but sarcoidosis should be considered in the differential diagnosis because steroid treatment can be effective.     

Sex-specific manifestations of Löfgren's syndrome

MOTIVATION: It has been debated whether patients need to have erythema nodosum to be classified as having L?fgren's syndrome. In this study, we have therefore in detail evaluated and compared a large number of patients with an acute onset of sarcoidosis and bilateral hilar lymphadenopathy (BHL), with or without erythema nodosum (EN). This study is important because it may lead to a more accurate definition of L?fgren's syndrome, and an exact phenotype of patients is crucial in modern medical research. BACKGROUND: L?fgren's syndrome is commonly regarded as a distinct clinical entity. METHODS: We have in detail evaluated a large group of patients (n = 150) with an acute onset of sarcoidosis with BHL, in most cases with fever, EN, and/or bilateral ankle arthritis or periarticular inflammation. Within this group, 87 patients had EN (EN positive), whereas 63 were without EN (EN negative), though with distinct symmetric ankle inflammation. RESULTS: EN-positive and EN-negative patients were identical in every aspect except that there were significantly more women in the EN-positive group: 58 women (67%) in the EN-positive group compared with only 17 (27%) women in the EN-negative group (p < 0.0001). In all other aspects, such as age, smoking habits, seasonal clustering of disease onset, rate of positive biopsies, chest radiography, pulmonary function, bronchoalveolar lavage cell distributions including the typically increased CD4/CD8 ratio, and clinical development of the disease, the EN-positive and EN-negative groups were close to identical. The two groups were also identically strongly associated with HLA-DRB1*0301/DQB1*0201, with 60 (69.0%) and 44 (69.8%) patients having this particular HLA type in the EN-positive and EN-negative groups, respectively. Such patients recovered to the same degree-that is, at almost 100%. CONCLUSIONS: We conclude that manifestations of L?fgren's syndrome differ between men and women, with EN found predominantly in women, whereas a marked periarticular inflammation of the ankles or ankle arthritis without EN is seen preferentially in men.     

Sarcoidosis or Sjögren syndrome? Clues to defining mimicry or coexistence in 59 cases

We present 5 new cases of coexisting sarcoidosis and Sj?gren syndrome (SS) and review the literature for additional cases in order to analyze the clinical, immunologic, and histologic characteristics that may help physicians differentiate the mimicry of SS by sarcoidosis from a true coexistence of both autoimmune diseases. We considered the coexistence of sarcoidosis with SS to be when patients presented specific histologic patterns of both diseases, simultaneously or at different times.Fifty-nine patients were included in the analysis (54 identified in the literature search plus our 5 unpublished cases): 49 (83%) patients were female and 10 (17%) were male, with a mean age at diagnosis of 50 years. According to the histopathologic examination of the exocrine glands performed in 53 cases, we defined coexistence of sarcoidosis and SS in 28 cases, while in the remaining 25 patients, sarcoidosis mimicked SS. Clues to identifying when sarcoidosis coexists with SS were a higher prevalence of systemic manifestations (arthritis and uveitis) and positive immunologic parameters (antinuclear antibodies, rheumatoid factor, and anti-Ro/SS-A), as well as the existence of a focal sialadenitis (Chisholm-Mason score grades III-IV, with a CD4+ lymphocytic infiltration) in the salivary gland biopsy. In patients first diagnosed with primary SS, the appearance of some clinical features such as hilar adenopathies, uveitis, or hypercalcemia leads to the diagnosis of coexisting sarcoidosis. A careful application of the new American-European consensus criteria had a sensitivity of 93% and a specificity of 92% in identifying when SS coexists with sarcoidosis.In conclusion, the association of sarcoidosis with SS leads to a true coexistence of both diseases in more than half the patients described in the literature, while in the remaining patients, sarcoidosis mimics SS. In light of these results, sarcoidosis should not be considered as an exclusion criterion for the diagnosis of SS, and in patients with a suspected overlap of the two diseases, application of the new American-European consensus criteria for diagnosis of SS should be mandatory.     

Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases.

The current authors aimed to quantify how the likelihood for a given diagnosis changes with the knowledge of bronchoalveolar lavage (BAL) cell differentials. As an initial estimate (a priori probability), frequencies of final diagnoses were taken. Using categorisations for cell differentials, a posteriori probabilities were then derived for each disease, according to Bayes. The analysis was performed in three of five groups of diagnoses suspected prior to BAL: interstitial lung disease (ILD; n=710), inflammatory disease (n=583), or lung tumour mimicking ILD (n=455). Overall, out of 1,971 patients, 18.3% had sarcoidosis, 7.7% usual interstitial pneumonia (UIP), 4.4% extrinsic allergic alveolitis (EAA), and 19.0% tumours. In the group with suspected ILD, the likelihood for sarcoidosis increased from 33.7 to 68.1% when lymphocyte numbers were 30-50% and granulocyte numbers were low; the likelihood for UIP increased from 15.8 to 33.3% when lymphocyte numbers were <30% with granulocytes elevated. CD4/CD8 was informative, especially in sarcoidosis and EAA. Despite considerable increases, the likelihood of rare diseases rarely reached appreciable values. Similar results were obtained in the other two groups of suspected diagnoses. In conclusion, these data suggest that bronchoalveolar lavage cell counts per se provide substantial diagnostic information only in relatively frequent diseases, such as sarcoidosis and usual interstitial pneumonia, and are less helpful in infrequent diseases.