Images in


William T. Shearer, MD, PhD,a Charlotte Cunningham-Rundles, MD, PhD,b Mark Ballow, MD,c Hans D. Ochs, MD,d and Raif S. Geha, MDe

Images in immunodeficiency
Editor’s note: This feature, Images in allergy and immunology, is designed to highlight current concepts of the immunopathology of allergic diseases and other common immunologically mediated diseases. The presentation will appear as sets of images that involve cross-pathology, histopathology, and molecular pathology and will cover a range of topics of interest to allergists and immunologists.
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.


This month’s issue of the Journal is devoted to the theme of primary immunodeficiency. Photos of patients both on the cover of the Journal and in this Images in Allergy article put faces on the diagnoses of immunodeficiency. As part of the rich tradition of medical education where students and residents follow

From athe Departments of Pediatrics and Immunology, Baylor College of Medicine and Texas Children’s Hospital, Houston; bMount Sinai Medical Center, New York, NY; cAllergy & Immunology Division, State University of New York at Buffalo and Women and Children’s Hospital of Buffalo; dthe Department of Pediatrics, University of Washington School of Medicine and Children’s Hospital and Regional Medical Center, Seattle; and eHarvard Medical School and Boston Children’s Hospital, Boston. Dr Shearer is supported by National Institutes of Health (NIH) grants AI27551, AI069441, AI36211, AI315714, HD41983, HD052102, HD17427, RR0188, HL079533, HL72705, HL78522, and RAT003084A and contract AI41089; the Pediatric Research and Education Fund, Baylor College of Medicine; and the David Fund, the Pediatrics AIDS Fund, and the Immunology Research Fund, Texas Children’s Hospital. Dr Ochs is supported by NIH grant HD17427, the Jeffrey Modell Foundation, the Immunodeficiency Foundation, and the DeJoria Wiskott-Aldrich Research Fund. Dr Geha is supported by NIH grant AI315714. Disclosure of potential conflict of interest: C. Cunningham-Rundles is on the advisory boards of Omrix, Baxter, and Talecris. M. Balow has received grant support from Nabi Biopharmaceutical and Bio Products Laboratories and is on the speakers’ bureau for AstraZeneca. The rest of the authors have declared that they have no conflict of interest. Received for publication August 14, 2007; accepted for publication August 17, 2007. Reprint requests: William T. Shearer, MD, PhD, Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, 6621 Fannin Street (MC-FC330.01), Houston, TX 77030. E-mail: J Allergy Clin Immunol 2007;120:982-4. 0091-6749/$32.00 Ó 2007 American Academy of Allergy, Asthma & Immunology doi:10.1016/j.jaci.2007.08.042

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.

teachers on patient rounds and witness the expression of human illness and its successful treatment, so, too, will we take the reader on the rounds of immunodeficient patients who have appeared in our clinics and hospitals. Many times, the appearance of patients tell us instantly what the diagnosis is, such as those with

October 2007


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.

FIG 5. NEMO deficiency. The characteristic appearance of NEMO deficiency is the conical teeth exhibited by this patient. NF-kB 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.


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 a-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.

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.

DiGeorge syndrome (Fig 1), hyper-IgE syndrome (Fig 2), Wiskott-Aldrich Syndrome (Fig 3), ataxia telangiectasia (Fig 4), and the nuclear factor-kB (NF-kB) essential modular (NEMO) syndrome (Fig 5). In other instances, the appearance of patients with appropriate clinical history directs us to select diagnostic tests, such as those with common variable

immunodeficiency (CVID) (Fig 6), severe combined immunodeficiency (SCID) (Fig 7), or chronic granulomatous disease (Fig 8). The power of immune reconstitution can be clearly appreciated by comparing the image of the sickly child with SCID (Fig 7) to the boisterous images of immune-reconstituted children with SCID on the cover of the Journal.


October 2007


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.

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 trimethoprimsulfamethoxazole, itraconazole, and IFN-g 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.

October 2007