Hemophagocytic lymphohistiocytosis associated with ataxia telangiectasia
Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory condition believed to be caused by uncontrolled activation of macrophages and histiocytes. HLH may be triggered by infections or associated with malignancy, metabolic disorders and drug toxicity, or alternatively, by a variety of genetic defects. While this disorder has been reported to be associated with a growing number of primary immunodeficiencies, especially those with significant T cell and (or) NK cell dysfunction, it has never been reported in ataxia telangiectasia (AT). AT is characterized by truncal ataxia, dilatation of blood vessels, immunodeficiency and a high predisposition to cancer. Almost all cases of AT have at least 1 or a combination of more than 1 of the following features: low immunoglobulin levels, inability to produce specific antibodies in response to vaccination, T cell lymphopenia and (or) T cell dysfunction. In this report, we describe the first case of a fatal episode of HLH in a patient with AT. The overlapping laboratory anomalies of HLH and lymphoid malignancy poses a challenge for accurate diagnosis, and awareness of the phenomenon by clinicians may result in earlier treatment and resolution of inflammation.
Statement of novelty: HLH can affect various types of immunodeficiency but has never been reported in patients with AT. Here, we report the first case of a fatal episode of HLH in a patient with AT.
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REFERENCES
Boder E. and Sedgwick R.P. 1958. Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 21:526–554.
Canman C.E. and Lim D.S. 1998. The role of ATM in DNA damage responses and cancer. Oncogene. 17:3301–3308.
Dalal B.I., Vakil A.P., Khare N.S., Wang S.Y., Richards M.J., and Chen L.Y. 2015. Abnormalities of the lymphocyte subsets and their immunophenotype, and their prognostic significance in adult patients with hemophagocytic lymphohistiocytosis. Ann. Hematol. 94:1111–1117.
Driessen G.J., Ijspeert H., Weemaes C.M., Haraldsson A., Trip M., Warris A., van der Flier M., Wulffraat N., Verhagen M.M., Taylor M.A., van Zelm M.C., van Dongen J.J., van Deuren M., and van der Burg M. 2013. Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasis and reduced immune repertoire diversity. J. Allergy Clin. Immunol. 131:1367–1375.e9.
Egeler R.M., Shapiro R., Loechelt B., and Filipovich A. 1996. Characteristic immune abnormalities in hemophagocytic lymphohistiocytosis. J. Pediatr. Hematol. Oncol. 18:340–345.
Feldmann J., Callebaut I., Raposo G., Certain S., Bacq D., Dumont C., Lambert N., Ouachée-Chardin M., Chedeville G., Tamary H., Minard-Colin V., Vilmer E., Blanche S., Le Deist F., Fischer A., and de Saint Basile G. 2003. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell. 115:461–473.
Goransdotter Ericson K., Fadeel B., Nilsson-Ardnor S., Soderhall C., Samuelsson A., Janka G., Schneider M., Gurgey A., Yalman N., Revesz T., Egeler R., Jahnukainen K., Storm-Mathiesen I., Haraldsson A., Poole J., de Saint Basile G., Nordenskjold M., and Henter J. 2001. Spectrum of perforin gene mutations in familial hemophagocytic lymphohistiocytosis. Am. J. Hum. Genet. 68:590–597.
Henter J.I., Elinder G., Soder O., and Ost A. 1991. Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis. Acta Paediatr. Scand. 80:428–435.
Henter J.I., Horne A., Arico M., Egeler R.M., Filipovich A.H., Imashuku S., Ladisch S., McClain K., Webb D., Winiarski J., and Janka G. 2007. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr. Blood Cancer. 48:124–131.
Henter J.I., Samuelsson-Horne A., Arico M., Egeler R.M., Elinder G., Filipovich A.H., Gadner H., Imashuku S., Komp D., Ladisch S., Webb D., and Janka G. 2002. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood. 100:2367–2373.
Janka G., Imashuku S., Elinder G., Schneider M., and Henter J.I. 1998. Infection- and malignancy-associated hemophagocytic syndromes: Secondary hemophagocytic lymphohistiocytosis. Hematol. Oncol. Clin. North Am. 12:435–444.
Janka G.E. 1983. Familial hemophagocytic lymphohistiocytosis. Eur. J. Pediatr. 140:221–230.
Janka G.E. 2007. Familial and acquired hemophagocytic lymphohistiocytosis. Eur. J. Pediatr. 166:95–109.
Micol R., Ben Slama L., Suarez F., Le Mignot L., Beauté J., Mahlaoui N., Dubois d’Enghien C., Laugé A., Hall J., Couturier J., Vallée L., Delobel B., Rivier F., Nguyen K., Billette de Villemeur T., Stephan J.L., Bordigoni P., Bertrand Y., Aladjidi N., Pedespan J.M., Thomas C., Pellier I., Koenig M., Hermine O., Picard C., Moshous D., Neven B., Lanternier F., Blanche S., Tardieu M., Debré M., Fischer A., and Stoppa-Lyonnet D. 2011. Morbidity and mortality from ataxia-telangiectasia are associated with ATM genotype. J. Allergy Clin. Immunol. 128:382–389.e1.
Nowak-Wegrzyn A., Crawford T.O., Winkelstein J.A., Carson K.A., and Lederman H.M. 2004. Immunodeficiency and infections in ataxia-telangiectasia. J. Pediatr. 144:505–511.
Puck J.M. 2012. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: The winner is T-cell receptor excision circles. J. Allergy Clin. Immunol. 129:607–616.
Savitsky K., Sfez S., Tagle D.A., Ziv Y., Sartiel A., Collins F.S., Shiloh Y., and Rotman G. 1995. The complete sequence of the coding region of the ATM gene reveals similarity to cell cycle regulators in different species. Hum. Mol. Genet. 4:2025–2032.
Staples E.R., McDermott E.M., Reiman A., Byrd P.J., Ritchie S., Taylor A.M., and Davies E.G. 2008. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene. Clin. Exp. Immunol. 153:214–220.
Stray-Pedersen A., Borresen-Dale A.L., Paus E., Lindman C.R., Burgers T., and Abrahamsen T.G. 2007. Alpha fetoprotein is increasing with age in ataxia–telangiectasia. Eur. J. Paediatr. Neurol. 11:375–380.
Suzuki K., Kodama S., and Watanabe M. 1999. Recruitment of ATM protein to double strand DNA irradiated with ionizing radiation. J. Biol. Chem. 274:25571–25575.
Wu X., Ranganathan V., Weisman D.S., Heine W.F., Ciccone D.N., O’Neill T.B., Crick K.E., Pierce K.A., Lane W.S., Rathbun G., Livingston D.M., and Weaver D.T. 2000. ATM phosphorylation of Nijmegen breakage syndrome protein is required in a DNA damage response. Nature. 405:477–482.
zur Stadt U., Schmidt S., Kasper B., Beutel K., Diler A.S., Henter J.I., Kabisch H., Schneppenheim R., Nurnberg P., Janka G., and Hennies H.C. 2005. Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11. Hum. Mol. Genet. 14:827–834.
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LymphoSign Journal
Volume 4 • Number 3 • September 2017
Pages: 113 - 116
History
Received: 7 July 2017
Accepted: 27 August 2017
Accepted manuscript online: 29 August 2017
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© 2017.
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MohammadAlsalamah and Chaim M.Roifman. 2017. Hemophagocytic lymphohistiocytosis associated with ataxia telangiectasia. LymphoSign Journal.
4(3): 113-116. https://doi.org/10.14785/lymphosign-2017-0007
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