Sections

Dermatologic Manifestations of Wiskott-Aldrich Syndrome

Sections Dermatologic Manifestations of Wiskott-Aldrich Syndrome
Overview
Presentation
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
References

Presentation

History

Thrombocytopenia and platelet dysfunction are often present from birth in Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome patients usually develop bleeding and bloody diarrhea during the first weeks or months of life. Hematuria, epistaxis, and cutaneous petechiae may appear.

The characteristic triad of thrombocytopenia, eczema, and recurrent infections generally becomes apparent during the first year of life.

Eczema usually appears during the first month and fulfills the Rajka and Hanifin diagnostic criteria for atopic dermatitis.

Recurrent bacterial infections begin in infancy as placentally transmitted maternal antibody levels diminish. Patients are susceptible to a wide variety of bacterial infections, including septicemia, pneumonia, meningitis, pansinusitis, conjunctivitis, furunculosis, otitis externa, and otitis media.

Physical Examination

Eczema commonly develops in the scalp, on the face, in the flexures, and in the diaper area, although patients commonly have widespread involvement with progressive lichenification. The lesion is essentially indistinguishable from atopic dermatitis apart from the frequent presence of purpura and/or petechiae and excessive bleeding from excoriations. Serosanguineous crust may appear. (See images below.)

Eczematous lesions in Wiskott-Aldrich syndrome. The lesion is essentially indistinguishable from that of atopic dermatitis except for the presence of purpura and petechiae.

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A bloody crust can be seen on the red papules.

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Immunoglobulin E (IgE)–mediated allergic diseases (eg, urticaria, food allergies, asthma) may appear.

Mucocutaneous petechiae may appear.

Spontaneous bleeding from the oral cavity and hematuria are common in Wiskott-Aldrich syndrome.

Secondary bacterial infection of eczematous lesions is common.

Hepatosplenomegaly is common in Wiskott-Aldrich syndrome.

Lymphadenopathy, transient arthritis, nephropathy, and nodular vasculitis are occasionally present in Wiskott-Aldrich syndrome.

Complications

With advancing age, T-cell function is progressively impaired, and patients are increasingly susceptible to infections caused by herpes and other viruses and Pneumocystis carinii.

Autoimmune phenomena may develop. Arthritis, renal disease, dermatomyositis, and autoimmune hemolytic anemia have been reported.

Lymphoreticular malignancy develops in 18-20% of patients, particularly in those with autoimmune manifestations. Non-Hodgkin lymphoma is the most common malignancy.^{[11, 12, 13, 14]}

Intracranial hemorrhage is a constant threat.

Differential Diagnoses

Bastida JM, Del Rey M, Revilla N, Benito R, Perez-Andrés M, González B, et al. Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia. Platelets. 2016 Nov 25. 1-4. [QxMD MEDLINE Link].
Derry JM, Ochs HD, Francke U. Isolation of a novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994 Aug 26. 78 (4):635-44. [QxMD MEDLINE Link].
Tyler JJ, Allwood EG, Ayscough KR. WASP family proteins, more than Arp2/3 activators. Biochem Soc Trans. 2016 Oct 15. 44 (5):1339-1345. [QxMD MEDLINE Link].
Guillén-Rocha N, López-Rocha E, Danielian S, Segura-Méndez N, López-González L, Lugo-Reyes SO. [Wiskott-Aldrich syndrome. A report of a new mutation]. Rev Alerg Mex. 2014 Jul-Sep. 61(3):219-23. [QxMD MEDLINE Link].
Silvin C, Belisle B, Abo A. A role for Wiskott-Aldrich syndrome protein in T-cell receptor-mediated transcriptional activation independent of actin polymerization. J Biol Chem. 2001 Jun 15. 276(24):21450-7. [QxMD MEDLINE Link].
Rivers E, Thrasher AJ. Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity. Eur J Immunol. 2017 Nov. 47 (11):1857-1866. [QxMD MEDLINE Link].
Pulecio J, Tagliani E, Scholer A, et al. Expression of Wiskott-Aldrich syndrome protein in dendritic cells regulates synapse formation and activation of naive CD8+ T cells. J Immunol. 2008 Jul 15. 181(2):1135-42. [QxMD MEDLINE Link].
Jia D, Gomez TS, Metlagel Z, Umetani J, Otwinowski Z, Rosen MK, et al. WASH and WAVE actin regulators of the Wiskott-Aldrich syndrome protein (WASP) family are controlled by analogous structurally related complexes. Proc Natl Acad Sci U S A. 2010 Jun 8. 107(23):10442-7. [QxMD MEDLINE Link]. [Full Text].
Perry GS 3rd, Spector BD, Schuman LM, et al. The Wiskott-Aldrich syndrome in the United States and Canada (1892-1979). J Pediatr. 1980 Jul. 97(1):72-8. [QxMD MEDLINE Link].
Conley ME, Wang WC, Parolini O, Shapiro DN, Campana D, Siminovitch KA. Atypical Wiskott-Aldrich syndrome in a girl. Blood. 1992 Sep 1. 80(5):1264-9. [QxMD MEDLINE Link].
Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES. Malignant lymphoma in patients with the Wiskott-Aldrich syndrome. Cancer Invest. 1985. 3(6):515-22. [QxMD MEDLINE Link].
Vignesh P, Suri D, Rawat A, Lau YL, Bhatia A, Das A, et al. Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome. Pediatr Blood Cancer. 2017 Jan. 64 (1):106-109. [QxMD MEDLINE Link].
Kritikou JS, Dahlberg CI, Baptista MA, Wagner AK, Banerjee PP, Gwalani LA, et al. IL-2 in the tumor microenvironment is necessary for Wiskott-Aldrich syndrome protein deficient NK cells to respond to tumors in vivo. Sci Rep. 2016 Aug 1. 6:30636. [QxMD MEDLINE Link].
Tanyildiz HG, Dincaslan H, Yavuz G, Unal E, Ikinciogulları A, Dogu F, et al. Lymphoma Secondary to Congenital and Acquired Immunodeficiency Syndromes at a Turkish Pediatric Oncology Center. J Clin Immunol. 2016 Oct. 36 (7):667-76. [QxMD MEDLINE Link].
Yamada M, Ariga T, Kawamura N, et al. Determination of carrier status for the Wiskott-Aldrich syndrome by flow cytometric analysis of Wiskott-Aldrich syndrome protein expression in peripheral blood mononuclear cells. J Immunol. 2000 Jul 15. 165(2):1119-22. [QxMD MEDLINE Link].
Zaninetti C, Gresele P, Bertomoro A, Klersy C, De Candia E, Veneri D, et al. Eltrombopag for the treatment of inherited thrombocytopenias: a phase 2 clinical trial. Haematologica. 2019 Jul 4. [QxMD MEDLINE Link].
Frączkiewicz J, Sęga-Pondel D, Kazanowska B, Ussowicz M. Eltrombopag Therapy in Children With Rare Disorders Associated With Thrombocytopenia. J Pediatr Hematol Oncol. 2019 Jun 12. [QxMD MEDLINE Link].
Sellars WA, South MA. Wiskott-Aldrich syndrome with 18-year survival. Treatment with transfer factor. Am J Dis Child. 1975 May. 129(5):622-7. [QxMD MEDLINE Link].
Mullen CA, Anderson KD, Blaese RM. Splenectomy and/or bone marrow transplantation in the management of the Wiskott-Aldrich syndrome: long-term follow-up of 62 cases. Blood. 1993 Nov 15. 82(10):2961-6. [QxMD MEDLINE Link].
Dupre L, Marangoni F, Scaramuzza S, et al. Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA-containing lentiviral vector and nonlethal irradiation. Hum Gene Ther. 2006 Mar. 17(3):303-13. [QxMD MEDLINE Link].
Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Díez IA, Dewey RA, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med. 2010 Nov 11. 363(20):1918-27. [QxMD MEDLINE Link]. [Full Text].
Williams DA. Curing genetic disease with gene therapy. Trans Am Clin Climatol Assoc. 2014. 125:122-9. [QxMD MEDLINE Link]. [Full Text].
Singh S, Khan I, Khim S, Seymour B, Sommer K, Wielgosz M, et al. Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector. Mol Ther Methods Clin Dev. 2017 Mar 17. 4:1-16. [QxMD MEDLINE Link].
Booth C, Romano R, Roncarolo MG, Thrasher AJ. Gene therapy for primary immunodeficiency. Hum Mol Genet. 2019 Jul 11. [QxMD MEDLINE Link].
Ferrua F, Cicalese MP, Galimberti S, et al. Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study. Lancet Haematol. 2019 May. 6 (5):e239-e253. [QxMD MEDLINE Link].
Candotti F. Gene therapy for Wiskott-Aldrich syndrome: here to stay. Lancet Haematol. 2019 May. 6 (5):e230-e231. [QxMD MEDLINE Link].
Corash L, Shafer B, Blaese RM. Platelet-associated immunoglobulin, platelet size, and the effect of splenectomy in the Wiskott-Aldrich syndrome. Blood. 1985 Jun. 65(6):1439-43. [QxMD MEDLINE Link].
Syrigos KN, Makrilia N, Neidhart J, Moutsos M, Tsimpoukis S, Kiagia M, et al. Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report. Ital J Pediatr. 2011 Sep 10. 37:42. [QxMD MEDLINE Link]. [Full Text].

Media Gallery

Eczematous lesions in Wiskott-Aldrich syndrome. The lesion is essentially indistinguishable from that of atopic dermatitis except for the presence of purpura and petechiae.
A bloody crust can be seen on the red papules.

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Author

Akimichi Morita, MD, PhD Professor and Chairman, Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Japan

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jacek C Szepietowski, MD, PhD Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

Sections Dermatologic Manifestations of Wiskott-Aldrich Syndrome
Overview
Presentation
DDx
Workup
Treatment
Medication
Questions & Answers
Media Gallery
References

Dermatologic Manifestations of Wiskott-Aldrich Syndrome Clinical Presentation

History

Physical Examination

Complications

References

Tables

Contributor Information and Disclosures

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