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Original article

Vol. 148 No. 1718 (2018)

Diffuse large B-cell lymphoma chemotherapy reveals a combined immunodeficiency syndrome in cartilage hair hypoplasia

  • Alexandre Nguyen
  • Nicolas Martin-Silva
  • Hubert de Boysson
  • Damaj Gandhi
  • Achille Aouba
DOI
https://doi.org/10.4414/smw.2018.14606
Cite this as:
Swiss Med Wkly. 2018;148:w14606
Published
24.04.2018

Summary

Cartilage hair hypoplasia (CHH) is a rare autosomal recessive ribosomopathy characterised by skeletal and integumentary system manifestations. It may also present with varied forms and intensities of haematopoietic and/or immune disorders. We report a 27-year-old female who presented a picture of combined immunodeficiency after receiving an adriamycin-based chemotherapy regimen followed by autologous stem cell transplantation. Her medical history indicated neonatal dwarfism, recurrent ear, nose and throat and respiratory infections, and hypogammaglobulinaemia, which were suggestive of a primary minor B-cell immune deficiency. Taken together, the diagnosis of cartilage hair hypoplasia was suspected and confirmed by means of molecular biological analysis. Here, we discuss the causal relationship and molecular mechanisms existing between both primary immunodeficiency and lymphoma conditions and between chemotherapy cytotoxicity and aggravation of the immune system and associated hematopoietic dysfunction, considering the role of all these components in light of the initially undiagnosed cartilage hair hypoplasia. Finally, this case highlights the importance of screening for primary immunodeficiencies in the setting of a diagnosis of lymphoma and/or dwarfism; moreover, CHH must be distinguished from other causes of small size; its diagnosis and complete check-up must include the molecular characterisation, and its management must be global in collaboration with haematologists, immunologists and internists.

References

  1. Ridanpää M, van Eenennaam H, Pelin K, Chadwick R, Johnson C, Yuan B, et al. Mutations in the RNA component of RNase MRP cause a pleiotropic human disease, cartilage-hair hypoplasia. Cell. 2001;104(2):195–203. doi:.https://doi.org/10.1016/S0092-8674(01)00205-7
  2. Riley P, Jr, Weiner DS, Leighley B, Jonah D, Morton DH, Strauss KA, et al. Cartilage hair hypoplasia: characteristics and orthopaedic manifestations. J Child Orthop. 2015;9(2):145–52. doi:.https://doi.org/10.1007/s11832-015-0646-z
  3. de la Fuente MA, Recher M, Rider NL, Strauss KA, Morton DH, Adair M, et al. Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2011;128(1):139–46. doi:.https://doi.org/10.1016/j.jaci.2011.03.042
  4. Kostjukovits S, Klemetti P, Föhr A, Kajosaari M, Valta H, Taskinen M, et al. High prevalence of bronchiectasis in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2017;139(1):375–8. doi:.https://doi.org/10.1016/j.jaci.2016.07.023
  5. Biggs CM, Kostjukovits S, Dobbs K, Laakso S, Klemetti P, Valta H, et al. Diverse Autoantibody Reactivity in Cartilage-Hair Hypoplasia. J Clin Immunol. 2017;37(6):508–10. doi:.https://doi.org/10.1007/s10875-017-0408-4
  6. Taskinen M, Ranki A, Pukkala E, Jeskanen L, Kaitila I, Mäkitie O. Extended follow-up of the Finnish cartilage-hair hypoplasia cohort confirms high incidence of non-Hodgkin lymphoma and basal cell carcinoma. Am J Med Genet A. 2008;146A(18):2370–5. doi:.https://doi.org/10.1002/ajmg.a.32478
  7. Bordon V, Gennery AR, Slatter MA, Vandecruys E, Laureys G, Veys P, et al.; Inborn Error Working Party of the European Bone Marrow Transplantation (EBMT) group. Clinical and immunologic outcome of patients with cartilage hair hypoplasia after hematopoietic stem cell transplantation. Blood. 2010;116(1):27–35. doi:.https://doi.org/10.1182/blood-2010-01-259168
  8. McCann LJ, McPartland J, Barge D, Strain L, Bourn D, Calonje E, et al. Phenotypic variations of cartilage hair hypoplasia: granulomatous skin inflammation and severe T cell immunodeficiency as initial clinical presentation in otherwise well child with short stature. J Clin Immunol. 2014;34(1):42–8. doi:.https://doi.org/10.1007/s10875-013-9962-6
  9. Aubert G, Strauss KA, Lansdorp PM, Rider NL. Defects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia. J Allergy Clin Immunol. 2017;140(4):1120–1129.e1. doi:.https://doi.org/10.1016/j.jaci.2016.11.051
  10. Gallimore CI, Lewis D, Taylor C, Cant A, Gennery A, Gray JJ. Chronic excretion of a norovirus in a child with cartilage hair hypoplasia (CHH). J Clin Virol. 2004;30(2):196–204. doi:.https://doi.org/10.1016/j.jcv.2003.10.007
  11. Kainulainen L, Lassila O, Ruuskanen O. Cartilage-hair hypoplasia: follow-up of immunodeficiency in two patients. J Clin Immunol. 2014;34(2):256–9. doi:.https://doi.org/10.1007/s10875-013-9981-3
  12. Horn J, Schlesier M, Warnatz K, Prasse A, Superti-Furga A, Peter H-H, et al. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia. Hum Immunol. 2010;71(9):916–9. doi:.https://doi.org/10.1016/j.humimm.2010.06.002
  13. Guggenheim R, Somech R, Grunebaum E, Atkinson A, Roifman CM. Bone marrow transplantation for cartilage-hair-hypoplasia. Bone Marrow Transplant. 2006;38(11):751–6. doi:.https://doi.org/10.1038/sj.bmt.1705520

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