Charles P. Darby

X-Linked Immunodeficiency with Increased IgM: Clinical, Ethnic, and Immunologic Heterogeneity

Summary: Two cases of immunodeficiency with increased IgM are reported. Patient 1 was a black male 3.5 years old who had recurrent pyogenic infections, failure to thrive, oral thrush, and systemic cryptococcal infection. Patient 2 was a 9-year-old white female who had recurrent cervical abscesses. Serum immunoglobulin determinations by radial immunodiffusion in both patients showed marked depression of IgG and IgA and marked elevation of IgM. A low molecular weight circulating monomeric IgM was demonstrated by immunoelectrophoresis and gel filtration in the second patient; this was not present in the first case. In vitro impairment of cellular immunity was observed in both patients. Administration of dialyzable leukocyte extracts (transfer factor) led to improvement of cell-mediated immunity in patient 1. The etiology of this syndrome apparently has several different genetic bases. These patients demonstrate heterogeneity in genetic, ethnic, immunologic, and other features of the syndrome.Speculation: The cause of hyper-IgM syndrome with depressed synthesis of IgA and IgG immunoglobulins is unknown. Deficiency in the function of T cells1 or a subpopulation thereof could have a causal relation to this syndrome, since there is increasing evidence that normal cellular immunity is necessary for the IgM-to-IgG “switch” in immunoglobulin production; whether it is also necessary for the formation of normal polymeric IgM from monomeric IgM is unknown, but this possibility merits speculation. In the present study, the occurrence of monomeric IgM in one patient but not the other, along with the differences in clinical manifestations, raises the possibility that the presence of monomeric IgM may be an index of a distinct subcategory of this syndrome with certain clinical features present only when the monomeric molecule is found. Our two patients, and all eight previously reported patients in whom isohemagglutinins were studied, had isohemagglutinins for A and B cells (i.e., were blood type O). In addition, two other hyper-IgM patients seen by us subsequently have been found to be blood type O (unpublished observation). If this phenomenon is universal, it would suggest a very close association between the blood group O antigen and this syndrome.

Congenital neutropenia. Report of a case and a biorationale for dental management.

Congenital neutropenia is characterized by a marked decrease in or lack of circulating PMNs in children with no prior history of drug intake. The neutropenia is persistent and the clinical course is one of early onset of severe, recurrent, and eventually fatal infections. Bone marrow studies show a maturation arrest of neutrophilic precursors. Because of their greatly increased susceptibility to infection, patients with congenital neutropenia present a difficult dental management problem. A case of congenital neutropenia has been presented, as well as a biorationale for dental treatment. On the basis of reports in the literature, the following recommendations for the management of patients with congenital neutropenia are made: 1. The prevention and control of infection and the interception of dental disease before surgical intervention becomes necessary should be the overriding considerations in the management of patients with congenital neutropenia. 2. The carious breakdown of teeth should be prevented by the daily application of a 0.4 per cent stannous fluoride gel in addition to oral hygiene and limitation of sucrose intake. 3. Periodontal therapy should be palliative only, since alveolar bone loss is progressive despite frequent oral hygiene instruction and prophylaxis. The goal of periodontal therapy for patients with congenital neutropenia should therefore be a decrease in gingival inflammation to make the patients mouth more comfortable and to slow down alveolar bone loss. Periodontal surgery is contraindicated. 4. Bacteremia and subsequent septicemia should be prevented since a minor infection can become life threatening in patients with congenital neutropenia. The patient should rinse for 30 seconds and the gingival sulci should be irrigated with a phenolated antiseptic mouthwash prior to all dental manipulations of the soft tissue. This will significantly reduce the incidence of bacteremia. 5. Surgery should be avoided if at all possible because of the high risk of post-operative infection. All surgery sholld be performed in the hospital, and the patient should be given antibiotics as determined by his physician. Primary closure should be done with fine polyglycolic acid sutures to reduce the chance of infection. If postoperative infection can be prevented, wound healing will progress normally despite the complete absence of PMNs.

Ischemia Following an Intragluteal Injection of Benzathine-Procaine Penicillin G Mixture in a One-Year-Old Boy

IN ENGLAND and Europe, eromolyn sodium (known there as disodium eromoglycate) has been used in the treatment of asthma for a number of years. This drug, derived from a plant long used for medicinal purposes in the Middle East, is unique for two reasons: 1) unlike all other antiasthma drugs, it is given prophylactically rather than after symptoms have already started; 2) it is administered in powder form by direct inhalation into the bronchial tree. How cromolyn sodium prevents an asthmatic attack is still unclear, though certain facts. are known. It certainly has no direct action on the bronchial mucosa or muscularis, and it has no known anti-inflammatory proper· ties. On the other hand it does interfere with the release of the chemical mediators of the allergic responses-such as histamine and SRS-A-from the sensitized mast cells which line the airways in the asthmatic lung. The type 1 antigen/antibody reaction which takes place on the surface of the mast cell still oc-

Proteus mirabilis brain abscess in a neonate.

Occasionally a brain abscess has been observed in a neonate. This report presents a unique case of a septic infant who developed a proteus mirabilis brain abscess shortly after birth, which persisted undetected until 2 1/2 months of age.

Successful immune reconstitution in severe combined immunodeficiency despite Epstein-Barr virus and cytomegalovirus infections

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV), frequently found in the acquired immune deficiency syndrome (AIDS), have been suspected of contributing to the latter immunodeficiency. The ability of normal HLA-identical sibling bone marrow to reconstitute an 8-month-old infant with severe combined immunodeficiency infected with these two viral agents is of interest. After presentation with severe mucocutaneous candidiasis, cavitary pulmonary disease, nodular cutaneous lesions, and hepatic abscesses containing acid-fast organisms, immunologic studies revealed lymphopenia, 1-3% T cells, and no lymphocyte responses to mitogens. Prior to transplantation, the infants blood B lymphocytes grew spontaneously in culture, suggesting they were infected with EBV. Indeed, an appropriate antibody response to EBV was detected at 2 months post-transplantation. At 3 weeks postgrafting, neutropenia and cholestatic jaundice developed without other signs of graft versus host disease. Liver biopsy demonstrated CMV but no EBV by DNA hybridization. There was evidence of T- and B-cell function by 2 weeks postgrafting, including vigorous in vivo and in vitro responses to candida. Although the blood lymphocyte T4:T8 ratio was inverted at 2 weeks, it reverted to normal by 6 weeks post-transplantation. All clinical disease resolved by 8 months and karotyping revealed all T and B lymphocytes to be XX. Thus, despite infections with both CMV and EBV, complete immunologic reconstitution was achieved in this, the most severe of all genetically determined immunodeficiency conditions, arguing against these viruses having a major role in the failure of bone marrow transplantation in AIDS.

Proteus Morganii Meningitis Treated with Trimethoprim-Sulfamethoxazole (Co-Trimoxazole)

* Associate Professor of Pediatrics, Infectious Disease Section, Medical University of South Carolina, Charleston, S.C. 29401. † Fellow in Pediatrics, Infectious Disease Section, Medical University of South Carolina. AALTHOUGH members of the genus Proteus are very common in nature, fortunately they seldom invade the cerebrospinal fluid. The species known as Proteus morganii has been well recognized as a cause of meningitis in neonates. It has also been a difficult organism to eradicate from the cerebrospinal fluid, thus giving rise to an extremely high morbidity and mortality in the neonate.1,2 After the neonatal period Proteus meningitis is unusual, being ordinarily associated with some congenital malformation allowing contamination of the cerebrospinal fluid from the exterior. A few instances have

CHRONIC GRANULOMATOUS DISEASE (CGD) IN A BLACK FAMILY WITH ATYPICAL GENETIC TRANSMISSION

We studied CGD in a Black family with three children, including a pair of identical twin sisters (10 yr.), DJ and SJ, and brother (13 yr.), BJ. SJ has had recurrent lung, liver abscesses, DJ recurrent pulmonary infections. BJ has always been in good health. DJ, SJ and BJ could not reduce NBT (.04, .03, .03 O.D.). Father (.16) and mother (.12) were normal (.14). Neutrophil auperoxide production was absent in twins (.00, .03, O.D.) and brother (.02). Mother (.13) was intermediate between control (.39), father (.34), and children. HMP activity for twins (31, 101 CPM) and brother (85 CPM) were well below control (1350), mother (1307) and father (1350). Neutrophils of twins and brother killed only 23%, 32% and 16% Staph. aureus after 2 hours (control 83%). Mother and father were normal. All had normal neutrophil MPO staining. Phagocytic neutrophil 02 consumption expressed in nanomoles/min/12×106 cells was DJ (.00), SJ (.01), and BJ (.00). Father (7.3) was normal (5.5). Mother (.77) was very low. Since children of both sex are affected, the mode of inheritance of CGD is not sex-linked. If the mode is autosomal recessive, the apparent absence of neutrophil dysfunction in the father suggests an undetectable carrier state. The unusual severity and frequency of infection in the female twins and the total absence of infection in the brother, a classic CGD, suggest a new variant of this syndrome.