A new hypothesis on the mechanism of digital clubbing secondary to pulmonary pathologies.

Our hypothesis concerns the chronic activation of macrophages, and the continual production of pro-fibrotic tissue repair factors, as a cause of digital clubbing in an array of pulmonary pathologies. The level of macrophage activation will differ between individuals, corresponding to the variable immune response to these pulmonary pathologies. Due to this variability, there is a corresponding inconsistency in the presentation of clubbing. Although testing of this hypothesis would be difficult, there is evidence to support our theory; including a link to chronic diseases involving granulomas, where there would be a large collection of macrophages present and pathologies in organs with large resident macrophage populations. This theory, therefore, could also be developed to include non-pulmonary causes of clubbing.

Clubbed fingers in a patient with inflammatory gingival hyperplasia.

The association of clubbing with miscellaneous diseases and its diagnostic implications are such that its detection should prompt consideration of the underlying etiology. We encountered a 48-year-old woman with clubbed fingers and a cauliflower-like gingival swelling on the hard palate of the upper jaw. There were no conventionally well-known causes for clubbing. Histological examination of gum biopsy specimen revealed a diagnosis of inflammatory gingival hyperplasia. As an etiology of clubbed fingers, gingivitis was suggested, since clubbing was regressed in parallel with remission of the gingivitis after the treatment by extraction of anterior teeth. Possible involvement of an autoimmune process in the pathogenesis was also considered, because of concomitant elevation of serum anti-double strand DNA antibodies. We recommend examination of the oral cavity for search of an inflammatory disease in cases with clubbed fingers, particularly when other common causes are not apparent.

Finger clubbing in children with human immunodeficiency virus infection.

We investigated the frequency of finger clubbing in 150 HIV-infected children consecutively hospitalized for acute pneumonia in South Africa and described associated clinical, laboratory and radiological features. Clubbing occurred in 30 of 150 (20%) HIV-infected children compared with one of 99 (1%) HIV-negative control patients, p < 0.001. Clubbing was associated with lower presenting heart and respiratory rates and enlarged parotid glands. Total and CD4 + lymphocytes, CD4:CD8 ratio and LDH were lower in children with clubbing, but serum protein and gammaglobulin were higher. No differences in the prevalence or type of microbial pathogens were found between the two groups. Clubbing was associated with a radiological diagnosis of LIP. Children with clubbing had a lower in-hospital mortality rate than those without clubbing (6.7% vs 24.2%, p = 0.035). In geographical areas with high HIV seroprevalence rates, the presence of clubbing in a child hospitalized for respiratory disease should raise the suspicion of HIV infection.

[Immunopathogenetic, endocrinologic and therapeutic problems of EMO syndrome. Observations based on a case report]. / Immunpathogenetische, endokrinologische und therapeutische Probleme des EMO-syndroms. Betrachtungen anhand einer Krankenbeobachtung.

The EMO-syndrome (thyroid acropachy) consists of the triad of exophthalmus, circumscribed pretibial myxedema and hypertrophic osteoarthropathy. The clinical picture is seen in thyroid disorders, as a rule occurring in hyperthyroidism, rarely in hypothyroid or euthyroid states. Our 47 year old female patient showed a hyperthyroidism in the beginning. The thyrostatic treatment resulted in a euthyroid stage. Serum antibodies against microsomal thyroid gland antigen with high titers were detected. The immunosuppressive treatment resulted in a titer reduction, but not in an improvement of the disease. The pathogenetical importance of the thyroid stimulating immunoglobulins and the role of aggressive and destructive antibodies against thyroid gland for the development of EMO-syndrome are discussed.

Hypertrophic osteoarthropathy, cutaneous vasculitis, and mixed-type cryoglobulinemia in a patient with nasopharyngeal carcinoma.

We describe a 27-year-old woman with a primary nasopharyngeal carcinoma who developed hypertrophic osteoarthropathy and cutaneous vasculitis. Her serum contained antibodies to Epstein-Barr virus and U1 RNP antigens. Cryoproteins isolated from her serum contained antibodies to U1 RNP and a protein with a molecular weight of 32 kd which reacted specifically with antibodies to U1 RNP. HLA typing revealed HLA-B7 and DR1; these have been reported to be increased in Japanese patients with rheumatic diseases who have autoantibodies to U1 RNP. These findings indicate that some features of the paraneoplastic syndrome in this patient might have been caused by immune complexes, part of which were formed by specific autoantibodies produced under genetically controlled conditions of immune responsiveness.

Role of immune complexes in hypertrophic osteoarthropathy and nonmetastatic polyarthritis.

Three case histories of patients with histologically proved malignant disease and an associated nonmetastatic symmetrical polyarthropathy are analysed. No evidence of a pathogenetic role for immune complexes was found in hypertrophic osteoarthropathy, whereas there is considerable evidence suggesting that the nonmetastatic polyarthritis associated with malignant lymphoma is an immune complex phenomenon.

Neurologic injuries, paraosteoarthropathies, and human leukocyte antigens.

The distribution of human leukocyte antigens (HLA) A and B has been evaluated in the circulatory lymphocytes of 68 patients with spinal cord injury and 32 with severe head injury. Paraosteoarthropathy (POA) was present in 43 spinal cord injury and 23 head injury patients. HLA-B 18 was found in 25.7% of the subjects with POA. Among 341 healthy subjects, the frequency of HLA-B 18 was 7.6%. There is a 0% frequency in patients without POA. The frequency of the HLA-B 18 antigen is significantly raised in POA patients, suggesting relationship between the development of POA and the presence of the HLA-B 18 marker. The presence of HLA-B 18 might be associated with an increased risk of POA in patients with lesion of the central nervous system.

Pachydermoperiostosis: studies on the synovium.

Pachydermoperiostosis (primary hypertrophic osteoarthropathy) is a familial disorder characterized by clubbing, periosteal bone changes, and furrowing of the skin. A 40 year old male with this syndrome and chronic arthritis was recently studied. The synovial fluid was non-inflammatory. Histologically the synovium exhibited hyperplasia and microvascular alterations. Immunofluorescent staining failed to identify deposits of immunoglobulin. Electron microscopy revealed multilayered basement laminae around small subsynovial blood vessels but no electron-dense deposits as described in studies of hypertrophic pulmonary osteoarthropathy. The pathogenesis is obscure and appears to be non-immunological.