Images in immunodeficiency William T. Shearer, MD, PhD, Charlotte Cunningham-Rundles, MD, PhD, Mark Ballow, MD, Hans D. Ochs, MD, Raif S. Geha, MD  Journal of Allergy and Clinical Immunology  Volume 120, Issue 4, Pages 982-984 (October 2007) DOI: 10.1016/j.jaci.2007.08.042 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 DiGeorge syndrome. The characteristic facies of infants with DiGeorge syndrome include widened epicanthal folds, flattened nasal bridge, short philtrum, recessed chin, rounded small mouth, and low set, posteriorly rotated ears with simplified helices. The photo was obtained for purposes of medical publication by Dr William T. Shearer with written parental permission for medical publication and with the collaboration of Dr Fabienne Dayer-Pastore, Texas Children's Hospital, Houston, Tex. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Hyper-IgE syndrome. Also known as Job syndrome, this immunodeficiency has a distinct facial expression with mild asymmetry, prominent jaw, and wide nasal ala. Eczematous skin lesions, recurrent staphylococcal skin infections, recurrent episodes of pneumonias often due to Staphylococcus aureus, pneumatoceles, and mucocutaneous candidiasis are common. Delayed shedding of primary teeth and skeletal abnormalities including severe scoliosis and recurrent pathologic fractures further characterize these patients. The morbidity of this disease varies, and some patients survive into adulthood, as did the patient pictured here. Written permission of the patient was obtained for use of this picture for medical publication through the courtesy of Dr Charlotte Cunningham-Rundles, Mount Sinai Medical Center, New York, NY, and the Immune Deficiency Foundation, Towson, Md. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Wiskott-Aldrich syndrome (WAS). Recurrent bacterial, fungal, and, in this case, viral (Herpes simplex) infections plague patients with WAS. Equally a problem is that of bleeding into eczematous skin lesions, mucosal surfaces, and other tissues because of concomitant thrombocytopenia and small platelet size. The long-term prognosis is complicated by an increased risk of malignancies and autoimmune disorders (see the Clinical Pearls article in this issue of the Journal). Dr Hans D. Ochs, University of Washington School of Medicine, Seattle, Wash, contributed this picture of the patient who died at 14 years of age. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Ataxia telangiectasia (AT). This patient demonstrates facial cellulitis and periorbital telangiectasias. The AT mutated gene produces pleiotropic changes in cellular response to radiation, cell cycle control, and intracellular transport of proteins that manifest themselves in choreoathetosis, cerebellar ataxia, susceptibility to malignancies, and humoral and cellular (T-cell) deficiency. Patients with AT frequently have greatly elevated serum levels of α-fetoprotein due to defective liver metabolism. Dr Hans D. Ochs, University of Washington School of Medicine, Seattle, Wash, contributed this picture of his patient who died at less than 10 years of age. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 NEMO deficiency. The characteristic appearance of NEMO deficiency is the conical teeth exhibited by this patient. NF-κB activation is impaired in this disorder, leading to ectodermal dysplasia (abnormal teeth, impaired sweating, thin hair) and immunodeficiency (hypogammaglobulinemia, specific antibody deficiency, impaired T-cell proliferation, and defective natural killer cell function). Dr Raif S. Geha, Harvard Medical School and The Children's Hospital, Boston, Mass, contributed this picture for use in medical publication with signed parental permission. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 CVID. The characteristic feature of CVID is the gradual loss of serum immunoglobulins and weakening T-cell immunity that usually begins in the second to third decade of life. Restoration of humoral immunity is made with regular treatments of intravenous or subcutaneous IgG. With this therapy, patients take back control of their lives and lead fulfilling productive careers. This patient is preparing for home infusion of IgG. Written permission for the use of this picture for medical publication was obtained through the courtesy of Charlotte Cunningham-Rundles, MD, PhD, Mount Sinai Medical Center, New York, NY, and the Immune Deficiency Foundation, Towson, Md. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 SCID. In contrast to the patients with SCID seen on the cover of this issue of the Journal, who all had bone marrow transplants, this patient typifies the wasted infant with SCID with failure to thrive and repeated infections. This patient has no human leukocyte antigen/mixed leukocyte culture matched siblings and at the time (circa 1970s) was not a candidate for a mismatched bone marrow transplant. This child succumbed to his infections. Photograph by Dr Mark Ballow at the State University of New York at Buffalo and Buffalo Children's Hospital, Buffalo, NY. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 8 Chronic granulomatous disease (CGD). This child represents the typical patient with CGD who suffers from infected seborrheic eczema, lymphadenitis, and pneumonia, primarily due to Staphylococcus aureus, Escherichia coli, and Aspergillus sp. Although prophylactic therapy with trimethoprim-sulfamethoxazole, itraconazole, and IFN-γ helps to reduce the number of infections in CGD, the concept of bone marrow transplantation and potentially gene therapy is gaining favor because of the morbidity and mortality of recurrent infections. Dr Hans D. Ochs, University of Washington School of Medicine, Seattle, Wash, contributed this picture of this child, now deceased. Journal of Allergy and Clinical Immunology 2007 120, 982-984DOI: (10.1016/j.jaci.2007.08.042) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions