Dr Ira Shah
M.D, DCH(Gold Medalist), FCPS, DNB

A one and a half month old boy born of non-consanguineous marriage presented with fever 11 days back followed by tonic convulsions and left sided lower motor neuron facial palsy for which he was admitted in a private hospital and diagnosed to have pyogenic meningitis in view of CSF showing 22 cells/cumm [3% polymorphs, 97% lymphocytes] with low sugar [10 mg/dl] and proteins of 55 mg%. He was treated with IV antibiotics and steroids. His Blood Bactec culture was negative. However, he subsequently developed diarrhea and respiratory distress since 3 days and referred for further management. His birth was uneventful and birth weight was 2.5 kg. He had been immunized for BCG and received one dose of oral polio vaccine. He was on exclusive breast feeds prior to his illness. On presentation, he was febrile and had tachypnea (respiratory rate = 64/min) with respiratory distress. Other systemic and general examination was normal. Investigations showed hemoglobin of 7.2 mg/dl, WBC count = 4,100/cumm (44% polymorphs, 56% lymphocytes) with normal platelet count. His C-reactive protein (CRP) was elevated (192 mg/dl) and X-Ray Chest showed left sided consolidation. Repeat CSF examination showed no cells with normal sugar and protein. He had deranged prothrombin Time (PT) and Partial Thromboplastin Time (PTT). Ultrasound (USG) chest showed minimal left sided pleural effusion. He was treated with IV antibiotics, IV fluids and oxygen but subsequently developed altered Ryle's Tube aspirate with hypotension and required fresh frozen plasma, blood transfusion and ionotropic support. He also developed pneumatoceles on left side with pneumothorax which required intercostal drainage (ICD) and ventilatory support. His pneumothorax resolved and ICD was removed after 15 days but pneumonia worsened. His Blood Bactec culture continued to be negative. In view of persistent pneumonia, he was investigated for underlying systemic disease. His serum alpha-1 antitrypsin levels were normal, stool for trypsin was positive and HIV ELISA was negative. Echocardiography was normal. Serum immunoglobulins after 1 month of antibiotics showed elevated IgM with normal IgA and IgG [IgM = 185 mg/dl (normal = 17-105 mg/dl), IgA = 27.8 mg/dl (Normal 2.8-47 mg/dl), IgG = 584 mg/dl ( Normal = 206-601 mg/dl)] suggestive of Hyper IgM syndrome. He was treated with intravenous immunoglobulin following which the pneumonia resolved. He was discharged on Trimethoprim-Sulphamethoxazole prophylaxis and advised to avoid live vaccines.

There are 5 immunoglobulin isotypes namely IgM, IgG, IgA, IgD and IgE. The B lymphocytes differentiate into immunoglobulin synthesizing cells (plasma cells) on exposure to an antigen and secrete IgM. The activated helper T cell binds with help of CD 40 ligand on the B-cell which leads to proliferation and immunoglobulin synthesis. In the primary immune response, usually only IgM antibody is made. Some B cells become memory cells and secondary immune response occurs whereby IgG, IgA and IgE antibodies are formed. In Hyper IgM syndrome, the B cells are unable to undergo isotype switching so that they produce only IgM as was seen in our patient. Our patient had a severe bacterial infection and when serum immunoglobulins done after 1 month of the illness, only IgM levels were elevated whereas IgG and IgA were normal suggestive of an abnormality of switch of IgM to IgG thus confirming the diagnosis of Hyper IgM.

Hyper IgM syndrome (HIGM) is a congenital primary immunodeficiency characterized by high serum IgM levels with normal to low levels of serum IgG and IgA. It is caused by defect in the CD40 ligand and interrupts B cell differentiation and switch of immunoglobulin M to other immunoglobulin isotypes. It is an X linked disorder seen predominantly in boys though may be also inherited as an autosomal recessive in heritance. Patients present with severe pyogenic infections including recurrent otitis media, sinusitis, pneumonia and diarrhea. Our patient presented with severe sepsis and pneumonia.

Treatment of HIGM consists of intravenous immunoglobulins (IVIg). Our patient responded only after he was given IVIg. Replacement IVIg and Trimethoprim-Sulphamethoxazole (TMP-SMX) prophylaxis are recommended. Curative treatment consists of bone marrow transplant.

Last updated: 01-05-2006