658 Ectodermal dysplacia associated with persistent combined immune deficiency

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Abstracts

Ectodermai Dysplasia Associated with PersisteFt Combined Immune Deficiency AM Rigalr, ME Paul, IC Hanson, SL Abramson, WT Shearer; HM Rosenblat? Baylor College of Medicine Ectodermal dysplasia (ED) is a group of rare disorders that present with diverse clinical features and characteristic defective development of the skin, nails and teeth. Although variable immune defects have been reported in association with ED, most abnormalities have been transient and no consistent pattern of defects has been described. We present a subject with ED and persistent T- and B- ceil abnormalities. The patient presented at 10 wo with a generalized papular erythematous rash, failure to thrive, Pneumocystis carinii pneumonia, and a history of Serratia marcescens bacteremia and meningitis at 6 wo and severe rotavirus gastroenteritis at 8 wo. The physical exam showed scant tonsillar tissue, slight hepatomegaly, and absent lymphadenopathy or splenomegaly. The family history was unremarkable except for the presence of skin hyperpigmentation in the mother and older sister compatible with Incontinentia Pigmenti. Initial immune evaluation revealed: normal serum IgG. IgA, and IgM; normal nitrobiue tetrazoiium test and CH50; and negative HIV serology. Lymphocyte phenotyping revealed normal percentages of CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD57+ NK ceils. Absolute numbers of all subsets were elevated due to a marked lymphocytosis ( ALC IO - 15 x IO”9 / L). In vitro lymphoproliferative responses (LPR) to PHA and ConA were markedly depressed (~5% of normal) and to PWM was 20% of normal and corrected partially with addition of exogenous IL-2 to cultures. LPR to Candida and streptokinase were absent. Adenosine deaminase, purine nucleoside phosphorylase levels and chromosomal analysis were normal. At 5 mo protein losing enteropathy developed with further failure to thrive and a fall in serum IgG to a nadir of 78 mg/dl (normal for age: 254-831 mg/dl). The lymphocytosis persisted with no significant change in lymphocyte subsets and modest improvement in LPR to PHA (20-40% of normal) and PWM (25 - 30% of normal) but continued marked depression of ConA induced LPR (5 -10% of normal). The enteropathy and malnutrition improved on TPN and an elemental diet and at 15 mo the clinical diagnosis of ED was made upon eruption of characteristic “conical teeth” and the other associated clinical features of heat intolerance with hyperthermia, anhydrosis, eczema and sparse fine hair. At present, 20 mo, there are no bone or nail abnormalities and in vitro lymphocyte studies remain stable with persistent moderate depression of LPR to PI-IA and PWM and significant depression of LPR to ConA. Immunization with bacteriophage phi X 174 between 19 and 20 mo showed poor primary and secondary responses and absent class switching to IgG antibody. This patient with a variant of ED demonstrates significant functional defects in T and B ceil immunity that have persisted in the face of iymphocytosis, relatively well preserved lymphocyte subset distribution, and correction of the early nutritional deficiencies. These lindings suggest a primary underlying immune defect in this variant of ED.

669 Non-caseating Sarcoid-Like Granuiomas of Spleen in a Sly/O Female With Pan-hypogammagiobuiinemia Charles Turnier, Donate110 GraBno, 7ina Zeecca, James Oleske UMDNJ,Hospital. Newark, NJ We describe the case of a 5iy/o female with pan-hypogammagiobuiinemia(common variable immunodeffrciency,CVID)diagnosed in 1993 on the basis of recurrent bacterial infections and low total IgG 284mg/d1(700-1700), IgM 15mg/dl (70-210). IgA 14.8(70-350).Her initial presentation included also a peculiar nodu-

J ALLERGY CLIN IMMUNOL JANUARY 2000

lar skin eruption biopsied by her dermatologist and diagnosed as pseudolymphoma. During that period, her clinical course was complicated by BOOP(bronchiolitis obliterans organizing pneumonia) diagnosed by BAL and bronchoscopy, for with she was treated with prednisone. At that time her chest x-ray showed reticula-nodular density in both lungs. Her pulmonary function studies demonstrated mild decreased in lung volumes(FVC 84%; FEVI 808)decrease in DLCO(IIO%). and her lung biopsy was compatible with the diagnosis of BOOP. Five years latershe developped persistent neutropenia and thrombocytopenia associated with significant splenomegaly,wich resolved after splenectomy. The pathology report of the spleen showed non-caseating granulomas, and negative stains for fungi and AFB. Other relevant laboratory result are: ACE 33u/l(normal range:8-52u/l); ESR Imm!hr;CT of chest: enlarged anterior mediastinal lymph nodes and fine interstitial pattern bilaterally. An ophtalmological exam revealed sarcoid-type nodular lesions in both eyelids, but sparing the eye. She was diagnosed with sarcoidosis, and the diagnosis was confirmed by the pathology department at Walter Reed Hospital in Washington DC. However, The normal ACE level is inconsistent with this diagnosis. Both Sarcoidosis and other types of non-caseating granulomas have been described in patients with pan-hypog-aglobulinemia. To the best of our knowledge, there is only one report of non-caseating granulomas in the spleen of a patient with CVID. It has been postulated by some ABPAU that these lesions represent an abnormal host response to antigens as well as potentially, a manifestation of a pre-malignant status. Increased awarness of this complication in patients with CVID is paramount in optimizing clinical management, implicating the need for increased surveillance to diagnose early lymphoid malignancies.

666 Grisceiii Syndrome: Another Immunodeficiency With Partial Aibinism and Neurological Involvement Cristina Miuki Abe Jacob*?, Eugenia Grill0 Carnide*f, Enilza EspreaficofS. Joao Carlos Bizariof, Ana Paula B.M. Castro*f, Angela B.E Fomin*f. Anronio Carlos Pasrorino*f *Institute da Crianca tuniversity of Sao Paulo,Brazil SMorphology Department,Medical School, Ribeirao Preto Griscelli Syndrome (GS) is a rare children disease characterized by pigmentary dilution, lymphohistiocytosis and immunodeficiency, besides visceralmegaly and neurological findings.The physical appearence ia a partial oculocutaneous albinism with silvery-gray hair color that is similar to Chediak-Higashi Syndrome. Immunological disorders includes: alteration in cell-mediated immunity, reduction of Natural Killer activity and variable humoral response. Recently, mutation of myosina-V gene has been founded in GS patients. The authors described 2 patients with GS that presented neurological involvement with convulsions and encephalopathy. Case 1 - SRS, 5 y, male, with consanguineous parents. He presented with fever, hepatospienomegaly, adenomegaly, and recurrent infections, with silvery-gray hair color. After two years evoluted with seizures and encephalopathy with rapid neurologic deterioration and death. Cell mediated immunodeficiency and reduction of NK cell were detected. Case 2: PO, 5y. male without consanguineous parents. This patient presented with fever, anemia, hepatosplenomegaly. and silvery-gray hair color. Since 3 years old developed encephalopathy and neurologic deterioration. In both cases their laboratorial tests revealed erytrophagocytosis and bone marrow and light microscopic examination of their hairs showed irregular clumps of pigment in melanocytes and little or no pigments adjacent keratinocytes. Analyses by molecular characterization of myosin-V is carried out in both patients. These cases empha-