Abstract
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Vasculitis occurs rarely in association with X-linked lymphoproliferative disease (XLP). There are four published cases of non-EBV XLP-associated cerebral vasculitis reported, none of whom have survived without major cognitive impairment.
Case
A 9-year old boy initially presented aged 5 years with a restrictive joint disease. He subsequently developed dysgammaglobulinemia, episodic severe pneumonitis, aplastic anaemia, gastritis and cerebral vasculitis. A diagnosis of XLP was made, based on flow cytometric analysis and the identification of a novel mutation in SH2D1A, c.96G>C. No peripheral blood lymphocyte clonal proliferation was identified and he was EBV negative, although human herpes virus-7 (HHV7) was detected repeatedly in his cerebrospinal fluid. He underwent a reduced intensity unrelated umbilical cord blood transplant, but failed to engraft. A second 5/6 matched cord gave 100 % donor engraftment. Complications included BK virus-associated haemorrhagic cystitis, a possible NK-cell mediated immune reconstitution syndrome and post-transplant anti-glomerular basement membrane disease, the latter treated with cyclophosphamide and rituximab. At +450 days post-transplant he is in remission from his vasculitis and anti-glomerular basement membrane disease, and HHV-7 has remained undetectable.
Conclusion
This is the second published description of joint disease in XLP, and only the fourth case of non-EBV associated cerebral vasculitis in XLP, as well as being the first to be successfully treated for this manifestation. This case raises specific questions about vasculitis in XLP, in particular the potential relevance of HHV-7 to the pathogenesis.
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References
Purtilo DT, Cassel CK, Yang JP, Harper R. X-linked recessive progressive combined variable immunodeficiency (Duncan’s disease). Lancet. 1975;1(7913):935–40.
Gholam C, Grigoriadou S, Gilmour KC, Gaspar HB. Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management. Clin Exp Immunol. 2011;163(3):271–83.
Pachlopnik Schmid J, Canioni D, Moshous D, Touzot F, Mahlaoui N, Hauck F, et al. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency). Blood. 2011;117(5):1522–9.
Tangye SG. XLP: clinical features and molecular etiology due to mutations in SH2D1A encoding SAP. J Clin Immunol. 2014;34(7):772–9.
Seemayer TA, Gross TG, Egeler RM, Pirruccello SJ, Davis JR, Kelly CM, et al. X-linked lymphoproliferative disease: twenty-five years after the discovery. Pediatr Res. 1995;38(4):471–8.
Booth C, Gilmour KC, Veys P, Gennery AR, Slatter MA, Chapel H, et al. X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease. Blood. 2011;117(1):53–62.
Kanegane H, Ito Y, Ohshima K, Shichijo T, Tomimasu K, Nomura K, et al. X-linked lymphoproliferative syndrome presenting with systemic lymphocytic vasculitis. Am J Hematol. 2005;78(2):130–3.
Talaat KR, Rothman JA, Cohen JI, Santi M, Choi JK, Guzman M, et al. Lymphocytic vasculitis involving the central nervous system occurs in patients with X-linked lymphoproliferative disease in the absence of Epstein-Barr virus infection. Pediatr Blood Cancer. 2009;53(6):1120–3.
Zhu J, Zhang Y, Zhen ZJ, Chen Y, Wang J, Cai RQ, et al. Lymphoma and cerebral vasculitis in association with X-linked lymphoproliferative disease. Chin J Cancer. 2013;32(12):673–7.
Palendira U, Low C, Chan A, Hislop AD, Ho E, Phan TG, et al. Molecular pathogenesis of EBV susceptibility in XLP as revealed by analysis of female carriers with heterozygous expression of SAP. PLoS Biol. 2011;9(11):e1001187.
Morra M, Simarro-Grande M, Martin M, Chen AS, Lanyi A, Silander O, et al. Characterization of SH2D1A missense mutations identified in X-linked lymphoproliferative disease patients. J Biol Chem. 2001;276(39):36809–16.
Yin L, Ferrand V, Lavoue MF, Hayoz D, Philippe N, Souillet G, et al. SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients. Hum Genet. 1999;105(5):501–5.
van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317.
Purtilo DT, Grierson HL, Davis JR, Okano M. The X-linked lymphoproliferative disease: from autopsy toward cloning the gene 1975–1990. Pediatr Pathol. 1991;11(5):685–710.
Toth B, Soltesz B, Gyimesi E, Csorba G, Veres A, Lanyi A, et al. Severe XLP phenotype caused by a novel intronic mutation in the SH2D1A gene. J Clin Immunol. 2015;35(1):26–31.
Liu HX, Tong CR, Wang H, Zhu J, Wang F, Cai P, et al. An analysis of etiological and genetic factors of a patient with familial hemophagocytic lymphohistiocytosis. Zhonghua Nei Ke Za Zhi. 2011;50(2):132–5.
Vrsalovic MM, Korac P, Dominis M, Ostojic S, Mannhalter C, Kusec R. T- and B-cell clonality and frequency of human herpes viruses-6, −8 and Epstein Barr virus in angioimmunoblastic T-cell lymphoma. Hematol Oncol. 2004;22(4):169–77.
Sirianni MC, Campagna M, Scaramuzzi D, Carbonari M, Toschi E, Bacigalupo I, et al. Control of human herpes virus type 8-associated diseases by NK cells. Ann N Y Acad Sci. 2007;1096:37–43.
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Gray, P.E., O’Brien, T.A., Wagle, M. et al. Cerebral Vasculitis in X-linked Lymphoproliferative Disease Cured by Matched Unrelated Cord Blood Transplant. J Clin Immunol 35, 604–609 (2015). https://doi.org/10.1007/s10875-015-0194-9
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DOI: https://doi.org/10.1007/s10875-015-0194-9