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Sarcoidosis and common variable immunodeficiency. A case of a malignant course of sarcoidosis in conjunction with severe impairment of the cellular and humoral immune system.

The occurrence of sarcoidosis in combination with common variable immunodeficiency (CVID) has been described in a small number of patients. In these patients, sarcoidosis consisted of lymphadenopathy, mild to moderate pulmonary involvement and hepatosplenomegaly. However, severe and rapidly progressive pulmonary fibrosis in combination with a severe defect of the cellular and humoral immune system has not been described yet. In our patient, defects of the T and B cell system resulted in severe immunodeficiency. The defect of the humoral immune system was characterized by the impairment of specific antibody production in vivo. In addition, hypogammaglobulinemia with missing IgA and IgE along with a marked defect in IgM and IgG production was noted. There was a progressively reduced lymphocyte proliferation in response to T cell mitogens, while proliferation after specific IL-2 stimulation was normal. A Th1 lymphocyte-subset-like profile might thus play a role in the pathogenesis and might form the connecting link between sarcoidosis and CVID. This is the report of a so far new and unique combination of severe immunodeficiency and sarcoidosis also associated with a congenital dysmorphia consisting of a palatal cleft. The findings of the 40 patients with CVID and sarcoidosis reported so far are discussed in order to point out the typical features of patients with this uncommon syndrome.

Adult↗

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. I. Enhanced capacity of bronchoalveolar lavage cells from patients with pulmonary sarcoidosis to induce angiogenesis in vivo.

Both allogeneic immunocompetent CD4+ lymphocytes and activated macrophages of mice can induce neovascularization when inoculated intradermally into host animals. Because sarcoidosis is associated with an increase in both activated macrophages and CD4+ effector lymphocytes in the lung, we carried out experiments in which cells obtained by bronchoalveolar lavage (BAL) of patients with pulmonary sarcoidosis were tested in a murine intradermal angiogenesis assay. BAL cells from patients with pulmonary sarcoidosis induced a significantly greater degree of angiogenesis than those from normal volunteers or from patients with other lung diseases. Moreover, the degree of angiogenesis induced by BAL cells from patients with sarcoidosis correlated positively with the severity of the disease. When BAL cells were separated into macrophage and lymphocyte subpopulations by flow cytometric techniques, the observed angiogenic activity was restricted primarily or exclusively to macrophages; lymphocytes were unable to induce angiogenesis in this xenogeneic assay system. These experiments suggest that pulmonary macrophages may play a role in the pathogenesis of sarcoidosis by inducing changes in the pulmonary microvasculature. Moreover, we hypothesize that these vascular changes may be induced not only in the lung but also in other organ systems such as skin, muscle, and eye in which microangiopathies are associated with sarcoid disease.

Animals↗

[Coincidence of silicosis and sarcoidosis. 2. Relations between silicosis and sarcoidosis as well as forensic consequences].

The observation of a coincidence of silicosis and sarcoidosis (see the 1st Communication) raises many problems on the pathogenesis of both diseases, their possible causal connections and not last the medical judgement. The mutual influence of both diseases is not discernible in the particular case. Pathogenetic connections derived from mentioned examples of coincidence of silicosis and sarcoidosis stay hypothetical, because its experimental confirmation cannot be realized. Within the medical judgement of the coincidence of silicosis and sarcoidosis the differentiation of injury caused only by silicosis must be tried. If that is not possible, the whole bodily injury must be imposed to silicosis to protect the patient from a disadvantageous expert opinion. The professional activity of patients with sarcoidosis in an atmosphere of quartz dust is not permissible, because the momentary injury of tissues of lung and lymph nodes as well as the prognosis of sarcoidosis are not definable with the actual available methods, but it is safe to say, that silicosis is an additional danger to the patient.

Dust↗

[Cardiac sarcoidosis with myopathy and advanced A-V nodal block in a woman with a previous diagnosis of sarcoidosis].

In 1992, a 49-year-old woman was admitted to the hospital because of exertional dyspnea. Three years earlier sarcoidosis had been diagnosed, and the patient was found to have bilateral hilar lymphadenopathy. The eye, skin, and knee joint were also involved. During the second hospital stay, atrial flutter with advanced A-V nodal block, scattered defects on a 201T1 scintigram, and marked cardiomegaly on chest roentgenogram led to the diagnosis of cardiac sarcoidosis. Signs and symptoms of cardiac failure subsided after placement of an artificial cardiac pacemaker, but the patient still complained of mild muscle weakness in the lower extremities on exertion. 67Ga scintigraphy revealed marked accumulation in the lower extremities, and muscle biopsy of the left gastrocnemius revealed numerous epithelioid cell granulomas with muscle fiber degeneration. Oral corticosteroid therapy was effective. A review of the 24 cases of sarcoid myopathy reported in Japan indicated that the male-to-female ratio is 1:3.8. As compared to patients in whom myopathy led to the diagnosis of sarcoidosis, those in whom myopathy developed after sarcoidosis was diagnosed were (1) relatively older, (2) more likely to have multiple organ involvement, and (3) more likely to have cardiac sarcoidosis. Corticosteroids were beneficial in about three quarters of these 16 cases, who received corticosteroid therapy.

Anti-Inflammatory Agents↗

Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of literature on skull sarcoidosis.

Bone sarcoidosis of the skull is an infrequent presentation of sarcoidosis. We describe a 51-year-old man who consulted due to inflammatory-appearing nodulation in the right supraorbital region. Images showed a solitary osteolytic lesion extending to soft tissues with increased scintigraphic uptake. The anatomopathological study revealed the presence of non-caseating epithelioid granulomas, compatible with sarcoidosis. Steroid treatment led to a marked remission of the lesion, without evidence of relapse during a follow-up period of 1 year. The literature dealing with skull sarcoidosis is reviewed.

Biopsy↗

Coexistence of sarcoidosis and myeloproliferative disease: a case of sarcoidosis preceding polycythaemia vera with a literature review.

A patient with the chronic active type of sarcoidosis developed polycythaemia vera 20 years later. A review of the literature shows that sarcoidosis preceding myeloproliferative disease tends to be of the chronic active variety. The same pattern is observed in associations of sarcoidosis with malignant lymphoproliferative disease and solid tumours, in which sarcoidosis appears to be the underlying cause of the subsequent malignancy.

Aged↗

Studies of bronchoalveolar lavage cells and fluids in pulmonary sarcoidosis. II. Enhanced capacity of bronchoalveolar lavage fluids from patients with pulmonary sarcoidosis to induce cell movement in vitro.

The ability to increase the motility of endothelial cells in vitro is a property common to most if not all angiogenesis-inducing factors. Because bronchoalveolar lavage (BAL) cells from patients with pulmonary sarcoidosis have an enhanced capacity to induce neovascularization, the BAL fluids from these patients were assessed for their effect on human and murine endothelial cells and fibroblasts obtained from a variety of tissue sources. A recently developed computer-assisted image analysis system was used to determine the extent and pattern of cell migration in a microwell screening assay. Data were obtained for BAL fluids from 10 patients with pulmonary sarcoidosis and from five normal volunteers. BAL supernatants from patients with active sarcoidosis showed an enhanced (2- to 8-fold) capacity to induce chemokinesis of both endothelial cells and fibroblasts, as measured by increased area of migration and polarized cell movement. There was a marked heterogeneity in the motility of cells from different organ origins, but enhanced cell movement was observed with both endothelial cells and fibroblasts. In contrast, BAL fluids from normal and sarcoid patients were similar in their effect on muscle cells and urothelial cells, whereas pericytes, which responded to BAL fluids from normal subjects or patients with nongranulomatous pulmonary disease, were inhibited by BAL fluids from patients with pulmonary sarcoidosis. The induction of endothelial cell movement in vitro induced by individual supernatants generally correlated with the capacity of BAL cells from these patients to induce angiogenesis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

HLA class I, II, and III polymorphism in Italian patients with sarcoidosis. The Pavia-Padova Sarcoidosis Study Group.

We studied the HLA polymorphisms (class I, II, and III) in 107 Italian patients with biopsy specimen-proven sarcoidosis in order to investigate the immunogenetic background of this disease. The mean age of onset of the disease was 36.08 +/- 12.4 years. Four patients (3.73 percent) were in radiologic stage 0, 38 patients (35.51 percent) were in radiologic stage I, 40 patients (37.38 percent) were in stage II, and 25 (23.36 percent) were in stage III. Thirty-eight patients (35.51 percent) had one or more extrapulmonary localization(s) of the disease. Positive association between sarcoidosis and HLA-B8 (chi 2 = 6.07, p = 0.0127, RR = 1.91) was confirmed. Regarding the age of onset of the disease, HLA-B35 was more frequent (chi 2 = 7.34, p = 0.0056, pc < 0.05, RR = 4.62) in patients with early onset of symptoms and/or signs, before the mean age of 36 years. With reference to the radiologic stage of the disease, HLA class II marker DR3 was more frequent in patients with stage I (chi 2 = 7.22, p = 0.0061, pc < 0.05, RR = 7.08). No significant relationship was found between sarcoidosis and HLA class III markers. These results seem to confirm an association of sarcoidosis with HLA classic genes and can sustain the hypothesis of a genetic heterogeneity of this disease.

Adult↗

Discrepancy between inducibility of ventricular tachycardia and activity of cardiac sarcoidosis. Requirement of defibrillator implantation for the inactive stage of cardiac sarcoidosis.

Monomorphic ventricular tachycardia (VT) developed in two patients with cardiac sarcoidosis. Before treatment with prednisolone, technetium or gallium scintigram revealed abnormal accumulation in the heart and bilateral hilar lymph nodes, but programmed electrical stimulation failed to induce VT in either case. Prednisolone was administered and the abnormal accumulation of the scintigra ms disappeared. However, VT became reproducibly inducible, and in one of the patients, transient entrainment was demonstrated in clinical VT morphology. Defibrillators were implanted in both patients. Some VTs associated with cardiac sarcoidosis are due to reentry, and inducibility of VT is not associated with the activity of cardiac sarcoidosis. Even though steroid therapy suppresses the activity of cardiac sarcoidosis, defibrillator implantation is necessary to prevent a possible arrhythmic event during the follow-up.

Adult↗

[Clinical course of ocular sarcoidosis in patients with histologically proven systemic sarcoidosis].

PURPOSE: We reviewed the clinical features, natural history and visual prognosis of 9 patients with histologically confirmed ocular and systemic sarcoidosis. PATIENTS: Nine patients underwent a follow-up study between 1993 and 1998. The diagnosis of sarcoidosis was supported by histological evidence of non caseating epithelioid-cell granuloma in tissue biopsy. RESULTS: The mean age was 40.912 years. The mean follow-up was 22.7 months (range 6 - 54 months). The ophthalmic involvement was bilateral in 8 patients. Before treatment, 3 eyes (17.6%) had a visual acuity less than 1/10. Two eyes (11.7%) had a visual acuity less than 3/10 and 10 eyes (58.8%) more than 6/10. The anterior uveitis was granulomatous in 2 eyes (11.7%) and non granulomatous in 8 eyes (47%). Five eyes (29.4%) had a pars planitis. The posterior segment manifestations of sarcoidosis were retinal vasculitis in 7 eyes (41.1%), papillitis in 10 eyes (58.8%) and choroidal granulomas in 2 eyes (11.7%). Seven patients were treated with systemic corticosteroids. One patient was treated with steroid eye-drops. After treatment, one eye (5.8%) had a visual acuity less than 1/10 and 13 eyes more than 6/10. After treatment, the choroidal granulomas disappeared and the intra-ocular inflammation was controlled in all cases. CONCLUSION: Although the number of patients in our series is small, the prognosis for ocular sarcoidosis appears to be good.

Adolescent↗

A sarcoidosis genetic linkage consortium: the sarcoidosis genetic analysis (SAGA) study.

BACKGROUND: Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results from an environmental insult in a genetically susceptible host. In the United States of America, African Americans have a higher sarcoidosis incidence and suffer greater morbidity than Caucasians. METHODS: A sarcoidosis genetic linkage study consortium was established to recruit African-American affected sib pair (ASP) families to identify chromosomal regions that may harbor sarcoidosis susceptibility genes and to determine if environmental factors modify any genetic effects. RESULTS: We successfully met our goal of enrolling 359 ASPs using a multifaceted recruitment approach. In the total 559 sib pairs that were enrolled, genetic analyses revealed incorrectly specified relationships that required reclassification or removal from the analysis dataset of 10.4% of reported full and 1.4% of reported half sib pairs. The final study sample comprised 415 full and 104 half sib pairs with complete data. This included 338 ASPs. Within sib pairs, affection status was not associated with sex. Only 15 per cent of the 229 families had three or more affected sibs, but they contributed 42 per cent of the ASP total. CONCLUSIONS: The SAGA study experience should provide useful lessons and information to serve others in conducting genetic studies of complex diseases in African-American families.

Black or African American↗

The chest radiograph and sarcoidosis. Reevaluation of the chest radiograph in assessing activity of sarcoidosis: a preliminary communication.

Classic radiographic staging of sarcoidosis, utilizing stages 0 through III, is a purely descriptive classification and bears no relation to the clinical activity of the disease. We propose a new method of determining sarcoidosis activity based solely on the chest radiograph. This "staging" is based on the presence or absence of air bronchograms, peribronchial cuffing, and subpleural thickening. Adenopathy, reticular, reticulonodular, and nodular opacities are not included in our methodology. Other diagnostic methods currently utilized for staging activity include Gallium scanning, bronchoalveolar lavage, and physiologic studies. In 85 studies performed in 51 patients with biopsy-proven sarcoidosis, this staging method agreed with Gallium scintigraphy results in 68.2%. The system failed in specific and identifiable subgroups of patients. We feel that the chest radiograph compares favorably with other staging methods in detecting the alveolitis phase of sarcoidosis, and is reproducible, noninvasive, and cost efficient.

Adult↗

[Sarcoidosis in Germany. Analysis of a questionnaire survey in 1992 of patients of the German Sarcoidosis Group].

In 1992, we performed a questionnaire study in patients, who are organized in the German Sarcoidosis Self-help group. The aim of our study was to analyze the state of diagnosis and therapy of sarcoidosis. In addition, patients were asked for their proposals to the physicians. We obtained valid answers from 651 patients. A high percentage of incorrect first diagnosis (in 37% as tuberculosis) seemed to be dependent on the insufficient use of bronchologic techniques and on the fact that in 19% of patients diagnosis was established only by chest x-ray. The diagnostic delay was estimated by the difference between the occurrence of the first clinical symptoms or x-ray findings and the final diagnosis of sarcoidosis and was on average (+/- SD) 2 +/- 5 years. Extrapulmonary manifestations were reported in 47% but histologically proven only in 30% of patients. 95% of treated patients had cortisone therapy, the median duration of therapy was 3.9 years. 19% of the patients underwent so-called alternative therapy concept (mostly immunostimulation) after lack of sufficient effect of cortisone treatment on symptoms and/or radiologic features. 12% of the patients were not treated at all. Familiar associations of sarcoidosis were reported by 49 patients. The patients asked for more research, more exchange of information, better education of students and physicians on this field and more interdisciplinary contacts.

Adolescent↗

[Long-term prognosis of pulmonary sarcoidosis. 2. Cardiac sarcoidosis and other extrapulmonary manifestations].

Frequency and prognostic importance of extrapulmonary manifestations have been examined in 254 patients with intrathoracic sarcoidosis. A follow-up was carried out after a median of 27 years from diagnosis. All patients could be traced. Extrapulmonary manifestations were found in 119 patients (47%), mostly occurring within the first years after diagnosis of intrathoracic sarcoidosis; skin manifestations were most frequently seen. ECG-abnormalities were found in 35 patients (14%); in 17 cases in the form of sinus tachycardia. No excess mortality was found (80 deaths observed versus 66 expected). The causes of death were related to sarcoidosis in 41%. Only tachycardia was associated with an unfavourable prognosis and this association vanished after adjusting for decreased lung function. None of the other extrapulmonary manifestations were associated with an unfavourable vital prognosis. Erythema nodosum was of no prognostic significance concerning survival. In conclusion, extrapulmonary manifestations are frequent in patients with intrathoracic sarcoidosis but do not influence vital prognosis.

Aged↗

Monocyte activating factor in sarcoidosis. I. Existence of the factor in sarcoidosis sera.

Sarcoidosis sera were found to have the ability to induce normal human monocytes to spread. Gel filtration of sarcoidosis sera on Sephadex G-200 showed that the factor mainly responsible for this activity had a molecular weight of about 70,000. The spreading factor also possessed the ability to increase all cell size of normal human monocytes as well as to increase their phagocytosis and glucose consumption. Accordingly, the spreading factor seems to be considered as a monocyte activating factor. Sarcoidosis sera showed a macrophage migration inhibitory activity, as well. On Sephadex G-200 column chromatography of the sera, the most obvious inhibitory activity was eluted in the fraction with a molecular weight of about 45,000. The macrophage migration inhibitory factor had the ability neither to increase cell size of normal human monocytes nor to increase their phagocytosis and glucose consumption.

Blood Glucose↗

[Use of talc and sarcoidosis - pathogenic role of cutaneous talc exposure in sarcoidosis].

INTRODUCTION: We report on two patients with sarcoidosis with disseminated nodes, who used talc on irritated cutaneous areas. CASE REPORT: A histologic examination with intense polarised light showed up cristalline bi-refringent particles within vessels in contact with granulomatous areas. Microdissection followed by an electronic microscopy study and microanalysis was realised. In situ microanalysis allowed us to identify bi-refringent particles with a size of roughly 0.25microm as silica or silicate coming possibly from talc. We consequently studied a brand name talc. The diffraction spectrum showed that this product not only contained talc but also chlorite and quartz. Electron microscopy examination showed particles of all sizes even smaller than 0.25microm. These infra-microscopic particles, visible in a vessel only when agglomerated, could be invisible under optic microscopy (resolution: roughly 0.5microm) inside the granuloma even though they are responsible for it. Moreover, at this level of size of particles, they may escape mineralogic analyses which use methods involving the destruction of organic material, the mineral residue collecting on cellulose filter with a diameter generally of 0.45microm. CONCLUSION: Two recent epidemiologic studies confirm the possible role of mineral exposure in sarcoidosis. Some sarcoidosis could be caused by mineral overload on genetically predisposed patients. Some cases could be related to mineral powder application. Among different types of mineral exposure, applications of cosmetic products may induce disseminated granulomatous reaction on genetically predisposed patients. Such applications have to be considered in epidemiologic studies.

Adult↗

Solitary spinal cord sarcoidosis without other manifestations of systemic sarcoidosis.

We report a biopsy-proven case of sarcoidosis limited to the spinal cord and responsive to treatment with oral corticosteroids. Involvement of the spinal cord by systemic sarcoidosis is uncommon and is associated with several unusual pathological and radiological characteristics that may contribute to its misdiagnosis and subsequent mismanagement. The importance of these unusual characteristics is greatly amplified in solitary spinal cord sarcoidosis because there are no systemic findings to suggest a sarcoid etiology.

Adult↗

Prostatic sarcoidosis. Review of genitourinary sarcoidosis.

Sarcoidosis is seen by the urologist only rarely but it may present a diagnostic and therapeutic dilemma. We describe a rare case of prostatic sarcoidosis. The literature relating to sarcoidosis throughout the genitourinary system is reviewed.

Adult↗