Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. The authors of this article present a case report of a 75-year-old, caucasian male patient previously subjected to examinations for secondary dementia and recurrent infections, which revealed paraneoplastic syndrome arose from thymoma. He underwent thymectomy, while his immunodeficiency syndrome sustained with frequent opportunistic infections, constantly requiring intravenous immunoglobulin treatment.
A case of histiocytic medullary reticulosis in a 45-year-old man is described. The presentation with a swinging pyrexia is typical. Associated features were very low levels of all immunoglobulins and proved disseminated intravascular coagulation. Heparin therapy was given and the difficulties of controlling such treatment are demonstrated. It is concluded that an increased awareness of the condition as a cause of pyrexia might lead to an improvement in prognosis.
The clinical and immunological aspects of 16 children with the syndrome of hypogammaglobulinaemia associated with normal or increased IgM (the hyper IgM syndrome) and their responses to treatment are reviewed. Increased concentrations of IgM, neutropenia, and recurrent infections could usually be controlled by antimicrobial and intravenous immunoglobulin treatment. Together with the bacterial infections characteristic of hypogammaglobulinaemia, these patients often developed opportunistic infections, including Pneumocystis carinii pneumonia, often presenting in the first year of life. The occurrence of sclerosing cholangitis, neurological complications, and neutropenia may be a result of an underlying cell mediated immune deficiency, autoimmunity, or infection. Despite a high incidence of opportunistic infections, immunological investigations did not show any abnormality of T cell function. These findings are discussed in the light of the recent demonstration that the lack of expression of a T lymphocyte activation antigen is the molecular basis of the X linked form of the disorder.
Patients with hypogammaglobulinaemia commonly receive regular long-term replacement therapy with a concentrate of pooled normal human immunoglobulin G (IgG) containing an organic mercury compound (thiomersal) as a preservative. In 26 such patients the total estimated mercury dosage received ranged from 4 to 734 mg (mean 157 mg) over treatment periods of six months to 17 years (mean 6.5 years). Nineteen patients (73%) had raised urine mercury concentrations, but no correlation was found between urine mercury and the age of the patient, the IgG dose, or the duration of treatment. Urine mercury concentrations are often used to control exposure and evaluate risks in exposed subjects. Hence most patients with hypogammaglobulinaemia are theoretically at risk from mercury exposure, although no clinical evidence of toxicity is yet apparent.
Fifty-five patients with late-onset idiopathic immunoglobulin deficiency were studied and upper or lower respiratory tract infections were encountered in about 90%. Cylindrical bronchiectasis was shown in all of the 21 patients in whom bronchograms were done. A thymoma was found in four patients. Three patients had diffuse interstitial pulmonary disease--two with proved and one with presumed lymphocytic interstitial pneumonitis. Five patients had no evidence of pulmonary disease, including two patients with long-standing late-onset immunoglobulin deficiency who had essentially no serum immunoglobulins. This small subgroup of patients with immunoglobulin dificiency without severe pulmonary infections cannot be explained in the context of current understanding of immunoglobulin deficiency. Thirty-two patients were followed up for long enough for the response to treatment to be assessed.
AIMS: To review the results of long term high dose intravenous immunoglobulin treatment. METHODS: 162 treatment years in 18 patients with hypogammaglobulinaemia who received intravenous immunoglobulin treatment between 1973 and 1993 were reviewed. RESULTS: A mean dose of 0.42 g/kg immunoglobulin resulted in a mean trough IgG concentration on the 23.5th centile for age. The subjects enjoyed a good standard of health. Infection rates were similar to the general paediatric population and a similar pattern of infections occurred. There were only 0.06 episodes of pneumonia and 0.11 hospital admissions per year of treatment. The development of chronic pulmonary disease was significantly related to trough IgG concentrations less than the 10th centile (p < 0.009), however, this developed in only two children after the start of treatment. All children had normal growth parameters. Adverse reactions to immunoglobulin infusions reduced from 9.1% to 0.8% after the introduction of low pH modified intravenous immunoglobulin in 1986. Although minor, transient increases in liver transaminase values were common; none of the 11 patients tested by hepatitis C polymerase chain reaction were positive. CONCLUSION: Children with hypogammaglobulinaemia who are receiving replacement treatment grow normally and have an infection rate similar to that of non-immunodeficient children. No evidence of transmission of hepatitis C virus by the Commonwealth Serum Laboratories immunoglobulin was found.
Iron, transferrin and ferritin were measured in serum samples from 16 patients with primary hypogammaglobulinaemia. Transferrin saturation was low in 12 patients (75%) and serum ferritin was low in 9 patients (56.25%). Both parameters were low, confirming the state of iron deficiency, in 6 patients (37.5%). These figures are highly significant (P less than 0.01) when compared with the prevalence of iron deficiency in the general population. Eight patients were maintained on intravenous immunoglobulin infusions and the rest on intramuscular immunoglobulin injections, their mean serum IgG being 4.4 g/l and 2.6 g/l respectively. There was no difference in the prevalence of iron deficiency between the two groups.
A case is reported of primary late-onset hypogammaglobulinaemia associated with a chronic seronegative, nonerosive arthritis, which was complicated by an episode of septic arthritis due to Mycoplasma pneumoniae. The patient had subcutaneous nodules which have not been regarded previously as a feature of the chronic arthritis associated with hypogammaglobulinaemia. The diagnosis of septic arthritis was delayed for 2 months until synovial fluid was specifically cultured for mycoplasmas. This delay resulted in considerable joint destruction. The importance of searching for mycoplasmas in similar cases is emphasised.
Arthritis may be the first clinical manifestation of primary hypogammaglobulinaemia. In 16 years of 281 patients who had immunodeficiency, 30 had arthritis at presentation. It was more common in Bruton's disease (15 (22%) of 69 patients) than in other forms of immunodeficiency (15 (7%) of 212 patients). Non-septic arthritis was more prevalent than septic arthritis, particularly monoarticular arthritis in Bruton's disease and pauciarticular disease in common variable immunodeficiency. Boys in whom a diagnosis of Bruton's disease was delayed were likely to develop recurrent infections complicated by arthritis. The measurement of serum immunoglobulin concentrations readily differentiates immunodeficiency from conditions such as Still's disease and dictates subsequent management.
A nurse with common variable hypogammaglobulinaemia was found to excrete a non-vaccine strain type II poliovirus for almost a year following a bout of gastroenteritis. Attempts were made to halt intestinal carriage of the virus in view of the possible risk of spread to immunocompromised patients and the risk of paralytic poliomyelitis to the patient himself. Three doses of killed Salk vaccine failed to stimulate salivary anti-polio antibodies. Excretion of the virus ceased spontaneously just before oral immunoglobulin containing high titres of antibodies to polio virus was used to halt virus excretion.
Here we describe a case of a secondary bronchiolitis obliterans organizing pneumonia (BOOP), which was associated with repeated respiratory infections caused by carbamazepine (CBZ)- induced hypogammaglobulinaemia. A 49-year-old woman had been treated with CBZ (400 mg/day). Two and a half years later, she developed of dyspnea with productive cough and high-grade fever. Chest roentgenogram and computed tomography showed bilateral infiltrates in lower lung fields. Her laboratory findings revealed severe hypogammaglobulinaemia, suggesting that an immune system disorder caused pulmonary infection. Histological examination by trans-bronchial lung biopsy (TBLB) demonstrated that many foamed alveolar macrophages were obstructing the alveolar ducts and adjacent alveoli, suggesting BOOP. After cessation of CBZ, the hypogammaglobulinaemia and chest roentgenogram findings markedly improved. The present case suggests that CBZ may have some adverse effects on the immune system and cause frequent airway infections, and that secondary BOOP could be induced by repeated infections caused by CBZ-induced hypogammaglobulinaemia.
Repeated pneumonia and hypogammaglobulinaemia was associated with long term low dose steroid therapy. Clinical improvement with restoration of antibody levels followed substitution of aerosol for oral therapy.
A 27-year-old man with severe infantile kyphoscoliosis suffered from recurrent respiratory tract infections during childhood and early adult life. He deteriorated and was found to have pernicious anaemia and common variable immunodeficiency with hypogammaglobulinaemia and impairment of cell-mediated immunity. Marked clinical improvement has followed the institution of effective gamma-globulin replacement.
Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months' treatment with the weekly intramuscular preparation and six months' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.
The case of a 17-year-old male with recurrent episodes of cellulitis affecting his left shin is presented. The cellulitis had been present on an intermittent basis over an 18-month period despite several courses of both intravenous and oral antibiotics. Each course of antibiotics resulted in a temporary remission, but on four occasions the cellulitis then relapsed. The patient was known to have pan-hypogammaglobulinaemia and was receiving intravenous IgG replacement therapy every 3 weeks. Other than cellulitis, he remained generally well. The organism responsible for the cellulitis was unknown until Campylobacter jejuni was grown in blood cultures during one of the relapse episodes. Based on microbial sensitivity, the patient was treated with ciprofloxacin. This resulted in full resolution of the cellulitis and he remains well. This case illustrates the value of blood cultures in helping microbial identification, particularly in immunocompromised patients with atypical infections.
Two brothers presented with unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation. They both developed eczema in infancy and have had recurrent infections. Additional physical findings in both boys included hypogonadism, flexion contractures, hypoplastic patellae, and scoliosis. Their facial similarity was striking with sloping foreheads, beaked noses, large, protruding ears, and micrognathia. Low levels of serum gammaglobulins and defective chemotaxis were present in both boys in infancy. The hypogammaglobulinaemia was transient and improved, reaching normal levels by 3 1/2 years and 15 months, respectively. Defective chemotaxis and recurrent infections have persisted to the present. Both parents were normal. The mode of inheritance was not clear, as both X linked and autosomal recessive patterns were possible. Although patients with congenital malformations who also had immunodeficiency have previously been reported, immune system abnormalities, especially those of a transient nature, may frequently go unrecognised.
Five patients with primary hypogammaglobulinaemia developed a severe polyarthritis that had some features in common with rheumatoid arthritis. Their joint disease could be distinguished from rheumatoid arthritis, however, by the dramatic improvement after gammaglobulin treatment. The arthritis of hypogammaglobulinaemia can, therefore, be included among the few potentially curable polyarthritides.
The patient, a 54-year-old housewife, was well until the age of 40 years when she developed repeated infections. During the next 10 years recurrent attacks of diarrhoea also appeared and were associated with weight loss, increased skin pigmentation, and later the occurrence of arthralgia and polyserositis. She was found to have deficiencies of IgG and IgA. A malabsorption syndrome was established and shown to be due to Whipple's disease by jejunal biopsy. She also had hypocalcaemia and osteomalacia. Weekly injections of human gammaglobulin had no effect on either the diarrhoea or the arthralgia, although the severity of respiratory infections was reduced. Intramuscular injections of vitamin D failed to restore the serum calcium to normal. Continuous oral tetracycline was followed by marked symptomatic improvement, disappearance of the diarrhoea and some weight gain. Steatorrhoea however persisted and the jejunal histology showed only slight improvement. The serum calcium returned to normal possibly as a result of correction of a magnesium deficiency. The relevance of the hypogammaglobulinaemia to the Whipple's disease is discussed, and a search of the literature shows six other cases where both disorders were associated.
A boy with congenital hypogammaglobulinaemia died at the age of 12 years after a viral meningoencephalitis of two and a half years duration due to an untypable picornavirus. He had received intravenous immunoglobulin every four weeks from the time of the start of immunoglobulin replacement treatment at the age of 3 years. The encephalitis did not respond to high dose intravenous gammaglobulin (2500 g during 22 months). The virus could not be isolated during the administration of intraventricular immunoglobulin (38.15 g) and intraventricular recombinant alpha interferon (121 X 10(6) units), but recurred rapidly each time intraventricular treatment was stopped. Further modes of treatment are still required for prevention and treatment of this disorder.
A neutropenic child of 20 months suffered generalized infection with Pseudomonas aeruginosa, involving the bloodstream and the meninges. This was successfully treated with intravenous and intrathecal antibiotics and granulocyte transfusions before granulopoiesis recovered spontaneously. No immunoglobulin replacement was given during the acute episode, as the diagnosis of X-linked hypogammaglobulinaemia was made subsequently.
Very few cases of acquired severe copper deficiency have been described. The principal effects are haematological, but the precise abnormalities are uncertain due to the possible association of other deficiencies. A case of isolated severe copper deficiency associated with late onset hypogammaglobulinaemia is reported in which the chief findings were macrocytic anaemia, neutropenia and a decrease in mean platelet volume. All these abnormalities resolved when copper therapy was instituted and recurred when the medication was stopped.
The microbial flora and some of its metabolites and enzymes in the stomach were compared in patients with achlorhydria, pernicious anaemia, and primary hypogammaglobulinaemia and in patients with dyspepsia with normal gastric acidity. Detailed analysis of the flora of the gastric juice and of the mucosa from the antrum, body, and fundus in six patients with hypogammaglobulinaemia (mean pH 8.2), seven patients with pernicious anaemia (mean pH 7.3), and five patients with dyspepsia (mean pH 1.9) yielded 22 different genera of bacteria, mainly from the patients with achlorhydria, the most common being streptococci, micrococci, staphylococci, veillonella, and lactobacilli. A similar flora was found associated with the mucosa at all three sites. Various metabolites were also looked for. beta Glucoronidase and C14 lipase were found in patients with hypogammaglobulinaemia but not in those with pernicious anaemia or dyspepsia. Volatile fatty acids were not found. Relatively high concentrations of ethanol were found in the patients with hypogammaglobulinaemia compared with those with pernicious anaemia (p = 0.02). Similar concentrations of dimethylamine were found in all three groups, but the concentrations of trimethylamine were much higher in patients with pernicious anaemia and hypogammaglobulinaemia. The high concentrations of some microbial enzymes and ethanol differentiated the group with hypogammaglobulinaemia from the rest, and these may bear some relation to the high incidence of gastric cancer in patients with hypogammaglobulinaemia.
Twelve patients with primary hypogammaglobulinaemia with diarrhoea not associated with known microbial pathogens were investigated. Histological evidence of inflammation was common in the stomach and jejunum. Moreover, eight of 10 patients undergoing colonoscopy had low grade 'microscopic colitis' with raised intraepithelial lymphocytes and an intact crypt architecture. Five of 12 patients had small intestinal inflammation on 111indium leucocyte scintigrams and all had increased faecal excretion (normal < 1%) of 111indium (over four days), which varied in intensity from mild (faecal excretion of 111indium = 1-3%) to that comparable with moderately active (7-14.5%) Crohn's disease. Three patients had small intestinal strictures superficially resembling Crohn's disease. Histologically, however, these lacked characteristic diagnostic features of Crohn's disease in two and the third patient had non-steroidal anti-inflammatory drug induced diaphragm like strictures. Six of seven who were most severely symptomatic were successfully treated with an elemental diet with rapid improvement of symptoms. The faecal excretion of 111indium was repeated in five and all improved but histologically the colitis remained unchanged. These studies show that some patients with primary hypogammaglobulinaemia have intestinal inflammation unlike that found in classic inflammatory bowel disease. Elemental diet is a useful temporary measure in the treatment of these patients.
OBJECTIVES--To study the occurrence of mycoplasmas and ureaplasmas in patients with hypogammaglobulinaemia and the relationship of these micro-organisms to septic arthritis. METHODS--Over a period of about 20 years, 53 men and 38 women with hypogammaglobulinaemia, most of whom were less than 50 years old, were examined clinically and microbiologically. Mycoplasmas and ureaplasmas were sought in the throat, urogenital tract and joints by standard cultural methods, although not consistently in the three sites of all patients. RESULTS--Arginine-hydrolysing mycoplasmas and ureaplasmas occurred with similar frequency in the sputum/throat of the hypogammaglobulinaemic patients, but no more often than might be expected in immunocompetent patients. Ureaplasmas, however, dominated in the urogenital tracts of both men and women, being found in 75% of vaginal specimens. Arginine-hydrolysing mycoplasmas occurred two to six times more frequently and ureaplasmas two to three times more frequently in urine specimens from hypogammaglobulinaemic patients than they did in such specimens from sex- and age-matched non-venereal disease, hospital patients or healthy subjects; these differences were statistically significant (p < 0.05). Enhanced mucosal colonisation probably increases the chance of spread to distant sites, such as the joints. Of the 91 patients, 21 (23%) had septic arthritis involving one or more joints. Mycoplasmas and/or ureaplasmas, but not bacteria, were isolated from the joints of eight (38%) of these patients. However, dissemination to joints apparently had not occurred in some despite the opportunity by virtue of mycoplasmal or ureaplasmal colonisation at a mucosal site. Sometimes antibiotic therapy failed clinically, and microbiologically and recommendations for management are outlined. CONCLUSIONS--Hypogammaglobulinaemic patients appear to be more susceptible to colonisation of mucous membranes, especially of the urogenital tract, with mycoplasmas and ureaplasmas than are immunocompetent individuals. These micro-organisms are responsible for about two fifths of the septic arthritides occurring in these patients.
Five patients with adult acquired hypogammaglobulinaemia, four of whom were achlorhydric, were studied. Jejunal bacterial counts were much higher than those in a control group of acid secretors, but were similar to those in a control group of patients with pernicious anaemia; Giardia lamblia were isolated from the jejunal content of all patients with hypogammaglobulinaemia. The concentration of conjugated bile acids in the fasting state was lower in hypogammaglobulinaemia than in pernicious anaemia, but in the two hypogammaglobulinaemic patients with steatorrhoea there was a normal bile salt response to a fatty meal.