The role of human leukocyte antigen in susceptibility and clinical manifestations of sarcoidosis

To investigate the association of human leukocyte antigen (HLA) with susceptibility and clinical manifestations of sarcoidosis. Fifty-five patients with sarcoidosis were studied by using allele group specific polymerase chain reaction technique (PCR). Our data show that: (1) the gene frequency of HLA-DR5 is significantly increased in patients with sarcoidosis, but that of HLA-DR7 decreased. (2) Gene frequencies of HLA-DR9 and HLA-DR5 are relatively increased in male patients and in patients with stage I and stage IIa, respectively. The results suggest that HLA-DR gene might contribute to the susceptibility as well as to the difference of clinical manifestations in sarcoidosis.     

Ileal ureter

Clinically apparent involvement of the heart and nervous system occurs in a relatively small number of patients with sarcoidosis. The diagnosis of myocardial and neurological sarcoidosis is difficult because anatomic presence of granulomas without clinical dysfunction is an important feature of sarcoidosis. The chest radiography is abnormal in 8 of every 10 patients with myocardial or neurosarcoidosis. Serum angiotensin-converting enzyme and gallium uptake studies may provide some indication of the extent and severity of the granulomatous process. Corticosteriods are the mainstay of therapy but chloroquine or hydroxychloriquine, methotrexate, and azathioprine are also effective. Prognosis of myocardial and neurological sarcoidosis is poor.     

Bullous sarcoidosis: a report of three cases

Three cases of pulmonary sarcoidosis presented as bullous emphysema with severe airflow obstruction, and the diagnosis of sarcoidosis was unsuspected for at least 2 years. Potential mechanisms of bullous emphysema from sarcoidosis are discussed. The physician should suspect sarcoidosis as the cause of bullous emphysema when young patients who have smoked relatively few pack-years present with emphysema or severe airflow obstruction. Additional clues are the presence of mediastinal adenopathy on a chest radiograph or a CT scan and a history consistent with extrapulmonary sarcoidosis.     

Detection and quantification of protein-losing enteropathy with indium-111 transferrin

BACKGROUND: Acid fast cell wall deficient forms (CWDF) of bacteria have been grown from blood, bronchial washings, and ocular anterior chamber fluid from patients with sarcoidosis. A monoclonal antibody raised against Mycobacterium tuberculosis whole cell antigen (H37RV) was used to characterise further CWDF grown from the blood of patients with sarcoidosis. METHODS: Blood from 20 patients with active sarcoidosis and from 20 controls was cultured using methods favourable for the growth of CWDF. Isolates were further characterised by indirect fluorescent antibody analysis using a monoclonal antibody highly reactive with M tuberculosis. RESULTS: CWDF were grown from the blood of 19 of 20 subjects with sarcoidosis. All isolates stained positively with the monoclonal antibody and with a modified Kinyoun stain. No organisms were grown from the blood of controls. CONCLUSIONS: These data demonstrate that CWDF can be grown from the blood of nearly all patients with active sarcoidosis. The results confirm that the organisms are mycobacterial in origin and are similar, if not identical, to M tuberculosis. Their role in the pathogenesis of sarcoidosis is unknown.     

Brain tumors in patients with Fanconi''s anemia

OBJECTIVES: To study whether an association between polyglandular autoimmune (PGA) syndrome type III [including autoimmune thyroid disease (ATD) and insulin-dependent diabetes mellitus (IDDM)], coeliac disease and sarcoidosis, exists. DESIGN: In patients with documented sarcoidosis, the presence of the disease constellation of ATD, IDDM and coeliac disease was examined. SETTING: The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, Lund University Clinics, General Hospital, Malm?, Sweden. SUBJECTS: Of all patients (n = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males, 34 females: median age at the time of the study 48 years, range 22-81 years: median observation time since the diagnosis of sarcoidosis 120 months, range 1-468 months) were examined in the present study. RESULTS: Amongst the 78 patients with documented sarcoidosis, one female patient was found with PGA syndrome type III, coeliac disease and sarcoidosis. CONCLUSIONS: This present patient further indicates the existence of an association between polyglandular autoimmune (PGA) syndrome type III, coeliac disease and sarcoidosis. To determine whether this disease constellation might constitute a new syndrome, further studies on larger groups of patients with sarcoidosis are demanded.     

Lung transplantation for pulmonary sarcoidosis

Patients with end-stage sarcoidosis have now undergone lung transplantation successfully with good short-term and intermediate-term results. Lung transplantation for sarcoidosis requires several considerations unique to this disease. Selection of pulmonary sarcoidosis patients for transplantation requires that medical therapy has been exhausted. This may involve the use of corticosteriods and alternative medications. Causes of pulmonary dysfunction other than pulmonary sarcoidosis, such as bronchiectasis and myocardial sarcoidosis, must be excluded before candidates are considered for transplantation. The extent and severity of extrapulmonary disease must also be assessed and may preclude lung transplantation. The presence of mycetomas is considered a relative contra-indication by some transplant centres and an absolute contra-indication by others. Relatively few patients with pulmonary sarcoidosis have undergone transplantation and, therefore, there are few data on outcome. Sarcoidosis frequently recurs in the allograft, but rarely causes symptoms or pulmonary dysfunction. More severe acute rejection episodes may occur in sarcoidosis transplant recipients, although at present there is no evidence of an increased risk of obliterative bronchiolitis or increased mortality.     

Psychosomatic aspects of sarcoidosis

Sarcoidosis is a multisystemic granulomatous disorder of unknown etiology. Several times pneumonologists described a remarkable personality of patients suffering from sarcoidosis. 44 patients with sarcoidosis were examined physically and psychosomatically. There are subgroups of patients, an important risk group shows long-lasting depressive features.     

Fluctuating currents in puncture therapy

Antibodies to Mycobacterium tuberculosis antigens H37Rv and reverse strains previously isolated from patients with sarcoidosis with granular isolates were determined in 50 patients with sarcoidosis (including 16 patients isolating granular types) and 56 patients with tuberculosis, by using ELISA and immunoblotting. Serum antibodies from patients with sarcoidosis were ascertained to more commonly react in ELISA with the antigen (ultrasound disintegrant (USDs) obtained from reverse mycobacteria isolated (initially) from patients with sarcoidosis (AGS) than with the USD of the M. tuberculosis H37Rv (AGT) and, on the contrary, serum antibodies from patients with tuberculosis more frequently reacted with the M. tuberculosis H37Rv. The spectrum of serum antibodies from patients with sarcoidosis greatly differed at immunoblotting with AGS and AGT. There was most commonly a reaction with the antigenic determinants 79, 27, 30, and 50 kDa to AGS and that of the determinants 17, 35, 32 kDa to AGT.     

Detection of antibodies to Borrelia species among patients with confirmed sarcoidosis in a region where Lyme disease is nonendemic

BACKGROUND: Lyme disease is a multisystemic disorder caused by the spirochete Borrelia burgdorferi, while sarcoidosis is a multisystemic granulomatous disease of unknown etiology. The purpose of this study was to evaluate the relationship between Lyme disease and sarcoidosis. METHODS: We examined the seroprevalence of antibody to Borellia species in patients with sarcoidosis. We performed the enzyme-linked immunosorbent assay, using three Japanese Borrelia species in addition to B. burgdorferi, and dotblot analysis using purified Borrelia-specific proteins in 38 patients with histopathologically confirmed sarcoidosis and 80 healthy controls. RESULTS: Two patients (5.3%) were positive for antibodies to Borrelia species according to one or both assays, and one (1.2%) healthy control was positive. In both patients it was suspected that Borrelia infection had developed prior to the development of sarcoidosis. CONCLUSION: Borrelia species were thought not to be responsible for the development of sarcoidosis in a nonendemic region in Japan. Since clinical manifestations of Lyme disease share certain similarities with those seen in sarcoidosis, ophthalmologists should be aware of the need to differentiate between the two diseases and the need for prompt treatment in each case.     

Diagnostic role of Mantoux test site biopsy in neurosarcoidosis

We discuss a patient with sarcoidosis presenting with cranial neuropathy and a cerebral mass lesion evident on imaging. Also, we review from the literature six patients with sarcoidosis presenting with cerebral mass lesion. We emphasize the diagnostic role of Mantoux test site biopsy in patients with dominant or isolated neurologic presentation because the involved sites are not easily accessible and Kveim's test antigen is not commercially available.     

Inducible expression of the 2-5A synthetase/RNase L system results in inhibition of vaccinia virus replication

Clinically apparent involvement of the nervous system occurs in a relatively small number of patients with sarcoidosis. The diagnosis of neurosarcoidosis is often difficult and particularly so in patients who lack either pulmonary or systemic manifestations of sarcoidosis. Furthermore, clinical features of neurosarcoidosis are extremely variable. In this series of 37 patients, seen during the last 30 years, cranial nerve palsies occurred in 52%, polyneuritis or polyneuropathy in 24%, meningeal involvement in 24%, muscle disease in 8%, and Guillain-Barré syndrome in 5% of the patients. Other presentations included seizures, brain mass, pituitary/hypothalamic syndrome, and memory loss associated with confusion. The chest radiograph was abnormal in 8 of every 10 patients with neurosarcoidosis. In 18 (85%) of 21 patients, gallium uptake was consistent with the diagnosis of active sarcoidosis. Serum angiotensin-converting enzyme levels were raised in about half of the patients. Cerebrospinal fluid features, including lymphocyte pleocytosis, raised protein levels, and decreased glucose concentration, were of little help. MRI with gadolinium enhancement was the most sensitive diagnostic tool, particularly in patients with meningeal involvement. The ultimate arbiter of the diagnosis of neurosarcoidosis, the presence of noncaseating granulomas in the involved tissue, was not always available. Although corticosteroids are the mainstay of therapy, in this series, 12 patients received chloroquine or hydroxychloroquine. Prognosis of chronic neurosarcoidosis is poor. Six (18%) of 37 patients died of complications related to sarcoidosis.     

Analysis of restriction fragment length polymorphism for the HLA-DR gene in Japanese patients with sarcoidosis

BACKGROUND: It is commonly assumed that some immunological disorder may play a part in the pathogenesis of sarcoidosis. Previous studies by several groups have shown a significant association with HLA-DR antigens in patients with sarcoidosis. In this study, restriction fragment length polymorphism (RFLP) analysis of the HLA-DR gene was designed to confirm the association at the gene level and to look for a gene rearrangement which may influence susceptibility to sarcoidosis. METHODS: Thirty two unrelated Japanese patients with sarcoidosis were tested for HLA antigens and subjected to RFLP analysis after digestion with Eco RI, Pst I, Bam HI, Pvu II, and Hind III by using an HLA-DR beta cDNA probe. A group of 47 unrelated healthy Japanese subjects served as controls. Frequencies of each restriction fragment were compared between the patients and the control subjects. Correlation between fragment frequencies and clinical features were also analysed. RESULTS: No restriction fragments of HLA-DR beta gene were found specific to the patients with sarcoidosis. The RFLP analysis could detect polymorphism of HLA-DR beta genes that was not distinguishable by conventional serological methods. Several restriction fragments of the DR beta gene were seen only in DRw52 positive individuals, and showed higher frequencies in the patients than in control subjects. The patients with these DNA fragments were likely to have limited stage disease with no ophthalmic involvement. CONCLUSIONS: An association between HLA and sarcoidosis was noted at the DNA level, although no restriction fragments were specific for this disease. RFLP analysis of the HLA gene is a more useful method than the usual HLA typing, and should be the first step in identifying the gene sequence which is connected with susceptibility to sarcoidosis.     

Vertebral sarcoidosis in adolescents

Two cases of vertebral sarcoidosis in pediatric patients are presented. All such patients reported have been black, 13-15 years old, and have a history of back pain. Radiographs of the involved vertebrae show primarily lytic destruction with sclerotic borders in some of the lesions. Fungal infections, tuberculosis, pyogenic osteomyelitis, Hodgkin's disease and metastatic disease must be considered in every patient with vertebral sarcoidosis.     

Extrapulmonary sarcoidosis

The clinical manifestations of sarcoidosis are extremely heterogeneous and overlap with a wide gamut of infectious and noninfectious granulomatous disorders. Prognosis of sarcoidosis is highly variable. Spontaneous remissions occur in nearly two thirds of patients, but chronic, progressive disease may result in severe sequelae. Fatalities occur in 1% to 4% of patients. Pulmonary manifestations typically dominate, but any organ can be affected. Skin, eye, and peripheral lymph nodes are each involved in 20% to 30% of patients. Clinically significant involvement of spleen, liver, bone, heart, kidney, or central nervous system occurs in 2% to 6% of patients. Asymptomatic involvement of these organs is far more common. We review the salient extrapulmonary features of sarcoidosis, and compare and contrast specific features that may mimic other etiologies.     

Clinical correlates of granulomas in muscle

We evaluated the clinical and myopathological features of all patients with granulomas in muscle biopsy specimens identified over a 5-year period (1992-1996) at the Washington University Medical Center. Ten patients were found to have granulomas in their muscle biopsy specimens. Of these, eight patients had myopathic changes. Seven had dysphagia as a major functional difficulty during the course of their disease. None had elevated levels of serum creatine kinase (CK). Four of the patients with myopathy had systemic sarcoidosis and relatively severe proximal weakness with functional disability. Treatment with corticosteroids was followed by marked improvement in strength and functional disability. The four other patients with myopathy had no systemic signs of sarcoidosis. Weakness was especially prominent distally in three of these patients. The two patients in this group treated with corticosteroids did not improve. The final two patients, who had granulomas in muscle but no myopathic changes, had clinical syndromes of mononeuritis multiplex and eosinophilic fasciitis (Shulman syndrome). We conclude that granulomatous myopathy, in the presence or absence of systemic sarcoidosis, is commonly associated with dysphagia (87%) and a normal serum CK. Clinical features in patients with sarcoidosis included severe proximal weakness with functional disability that often responded to corticosteroid treatment. Granulomatous myopathy without systemic sarcoidosis was associated with milder, but more predominantly distal weakness.     

Noninvasive assessment of the direct action of oral nifedipine and nicardipine on left ventricular contractile state in patients with systemic hypertension: importance of reflex sympathetic responses

BACKGROUND: Alveolar macrophages from patients with sarcoidosis were analyzed for their ability to secrete tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1-beta), and interleukin-6 (IL-6). RESULTS: Constitutive release of all three monokines in these patients was concomitantly increased in the active state of disease in comparison with inactive sarcoidosis or healthy control subjects. Alveolar macrophages from patients with inactive sarcoidosis compared with cells from healthy subjects showed increased spontaneous secretion of TNF-alpha and IL-6 only, whereas the constitutive release of IL-1-beta was similar as in healthy volunteers. In vitro stimulation of alveolar macrophages from healthy control subjects with lipopolysaccharide or pokeweed mitogen led to a time- and dose-dependent enhanced secretion of TNF-alpha, IL-1-beta, and IL-6. In a similar manner, with corresponding cells from patients with sarcoidosis the secretion of all three cytokines could be further increased by stimulation with lipopolysaccharide or pokeweed mitogen. CONCLUSIONS: The data presented indicate that an increased release of TNF-alpha, IL-1-beta, and IL-6 correlates to disease activity and may play a critical part in the pathogenesis of sarcoidosis.     

A sequence in the 5'' flanking region confers progestin responsiveness on the human c-myc gene

Sarcoidosis is a systemic granulomatous disease of undetermined etiology in which the immune system is overstimulated. Management of the patient with sarcoidosis entails continuity of patient care far beyond disease, even into remission. Care is comprehensive, including all involved organ systems, coordination of specialty consultations and services, and includes diagnostic tests. Therapeutic decisions are the responsibility of the primary care practitioner. Prognosis of sarcoidosis is not uniformly good. Patients can die. Subacute sarcoidosis patients usually do not require pharmacologic therapy. Chronic sarcoidosis may require long-term treatment for years to indefinitely. Corticosteroids are still the drugs of choice and other therapy is now available. Health organizations and private nonprofit support groups are available for patient education and assistance. Close support must still come from the family unit. Sarcoidosis may occur in family members in different cohorts at all ages in life and in any racial or ethnic group. The second in a two-part series on management of the patient with sarcoidosis, this article describes coordination of care and considers community, prevention, and family aspects of the disease.     

Reemployment of patients with surgical salvage of open, high-energy tibial fractures: an outcome study

The association of soft tissue and bone sarcoidosis in the hand and wrist is rare. Two cases of sarcoidosis, 1 with involvement of the distal radius and both flexor and extensor tendons in the wrist and another with tenosynovitis of 2 fingers associated with phalangeal osteolysis, are reported. Both patients were surgically treated by tenosynovectomy. The importance of the systemic corticosteroid therapy is emphasized.     

Corticosteroid therapy in cardiac sarcoidosis

Corticosteroid treatment of cardiac sarcoidosis is not conclusive, although sarcoid granulomas in the heart may be more responsive to steroid therapy than in other organs. Healing of sarcoidosis lesions in the heart results in fibrosis and sinning of the myocardium, which may lead to aneurysm formation causing congestive heart failure or sudden death. Congestive heart failure is the leading cause of death in patients with cardiac sarcoidosis in Japan. It is reasonable to initiate steroid therapy as soon as the diagnosis of cardiac sarcoidosis is established in order to prevent fibrosis. Early initiation of steroid therapy with conventional treatment for specific cardiac manifestations (antiarrhythmic therapy, pacemaker implantation and heart failure medication) should bring improvement in the left ventricular systolic and diastolic function with prevention from malignant arrhythmias. Systemic disorder represents a contraindication to organ transplantation, but heart transplantation is now a feasible treatment for patients with end-stage cardiac sarcoidosis with congestive heart failure.     

The Norwegian Polio Study 1994: a nation-wide survey of problems in long-standing poliomyelitis

BACKGROUND: Sarcoidosis is a multisystemic granulomatous disease of unknown etiology, while Lyme borreliosis is a multisystemic disorder caused by Borrelia burgdorferi. The purpose of this study is to evaluate the relationship between sarcoidosis and Lyme borreliosis in a region of Japan where Lyme borreliosis is endemic. METHODS: We determined the seroprevalence of anti-Borrelia burgdorferi antibodies as well as antibodies three Japanese Borrelia strains by enzyme-linked immunosorbent assay and dotblot assay using purified Borrelia-specific proteins in 46 patients with confirmed sarcoidosis and 150 controls (50 disease controls and 100 healthy controls) in Hokkaido, the affected region. RESULTS: Fifteen patients with sarcoidosis (32.6%) tested positive for Borrelia spirochete in both assays, compared with two disease controls (4.0%) and two healthy controls (2.0%). The seroprevalence of anti-Borrelia antibodies in patients with sarcoidosis was much higher in the affected region than in the region in our previous study were Lyme borreliosis is non-endemic. CONCLUSION: In a region where Lyme borreliosis is endemic, Borrelia infection may be partially associated with sarcoidosis.