Which dietary modifications are used in the treatment of autoimmune lymphoproliferative syndrome (ALPS)?

Answer

No specific diets, dietary supplements, or dietary avoidances have been shown to have a significant effect on the course of ALPS.

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Rieux-Laucat F, Magérus-Chatinet A, Neven B. The Autoimmune Lymphoproliferative Syndrome with Defective FAS or FAS-Ligand Functions. J Clin Immunol. 2018 Jul. 38 (5):558-568. [Medline].
Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, et al. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995 Jun 16. 81 (6):935-46. [Medline].
Haslett C, Savill J. Why is apoptosis important to clinicians?. BMJ. 2001 Jun 23. 322 (7301):1499-500. [Medline].
Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26. 356 (6367):314-7. [Medline].
Sneller MC, Straus SE, Jaffe ES, Jaffe JS, Fleisher TA, Stetler-Stevenson M, et al. A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease. J Clin Invest. 1992 Aug. 90 (2):334-41. [Medline].
Bride K, Teachey D. Autoimmune lymphoproliferative syndrome: more than a FAScinating disease. F1000Res. 2017. 6:1928. [Medline].
Martínez-Feito A, Melero J, Mora-Díaz S, Rodríguez-Vigil C, Elduayen R, González-Granado LI, et al. Autoimmune lymphoproliferative syndrome due to somatic FAS mutation (ALPS-sFAS) combined with a germline caspase-10 (CASP10) variation. Immunobiology. 2016 Jan. 221 (1):40-7. [Medline].
Oliveira JB, Bidère N, Niemela JE, Zheng L, Sakai K, Nix CP, et al. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci U S A. 2007 May 22. 104 (21):8953-8. [Medline].
Bristeau-Leprince A, Mateo V, Lim A, Magerus-Chatinet A, Solary E, Fischer A, et al. Human TCR alpha/beta+ CD4-CD8- double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vbeta TCR diversity and are clonally related to CD8+ T cells. J Immunol. 2008 Jul 1. 181 (1):440-8. [Medline].
Brandt D, Hedrich CM. TCRαβ⁺CD3⁺CD4^-CD8^- (double negative) T cells in autoimmunity. Autoimmun Rev. 2018 Apr. 17 (4):422-430. [Medline].
Tarbox JA, Keppel MP, Topcagic N, Mackin C, Ben Abdallah M, Baszis KW, et al. Elevated double negative T cells in pediatric autoimmunity. J Clin Immunol. 2014 Jul. 34 (5):594-9. [Medline].
Hossny EM, et al. Double negative alpha beta T cells in pediatric hemophagocytic syndromes. Egypt J Pediatr Allergy Immunology. 2019. 17(1):13-19.
Neven B, Magerus-Chatinet A, Florkin B, et al. A survey of 90 patients with autoimmune lymphoproliferative syndrome related to TNFRSF6 mutation. Blood. 2011 Nov 3. 118 (18):4798-807. [Medline].
Neven B, Bruneau J, Stolzenberg MC, et al. Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients. Blood. 2014 Sep 4. 124 (10):1597-609. [Medline].
Fleisher TA. The autoimmune lymphoproliferative syndrome: an experiment of nature involving lymphocyte apoptosis. Immunol Res. 2008. 40 (1):87-92. [Medline].
Price S, Shaw PA, Seitz A, Joshi G, Davis J, Niemela JE, et al. Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations. Blood. 2014 Mar 27. 123 (13):1989-99. [Medline].
Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014. 5:162. [Medline].
Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM, et al. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002 Sep 26. 419 (6905):395-9. [Medline].
Bolze A, Byun M, McDonald D, Morgan NV, Abhyankar A, Premkumar L, et al. Whole-exome-sequencing-based discovery of human FADD deficiency. Am J Hum Genet. 2010 Dec 10. 87 (6):873-81. [Medline].
Takagi M, Shinoda K, Piao J, Mitsuiki N, Takagi M, Matsuda K, et al. Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation. Blood. 2011 Mar 10. 117 (10):2887-90. [Medline].
Shiota M, Yang X, Kubokawa M, Morishima T, Tanaka K, Mikami M, et al. Somatic mosaicism for a NRAS mutation associates with disparate clinical features in RAS-associated leukoproliferative disease: a report of two cases. J Clin Immunol. 2015 Jul. 35 (5):454-8. [Medline].
Calvo KR, Price S, Braylan RC, Oliveira JB, Lenardo M, Fleisher TA, et al. JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities. Blood. 2015 Apr 30. 125 (18):2753-8. [Medline].
Chiocchetti A, Indelicato M, Bensi T, Mesturini R, Giordano M, Sametti S, et al. High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation. Blood. 2004 Feb 15. 103 (4):1376-82. [Medline].
Clementi R, Chiocchetti A, Cappellano G, Cerutti E, Ferretti M, Orilieri E, et al. Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function. Blood. 2006 Nov 1. 108 (9):3079-84. [Medline].
Michalovich D, Nejentsev S. Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy. Front Immunol. 2018. 9:369. [Medline].
Kuehn HS, Niemela JE, Rangel-Santos A, Zhang M, Pittaluga S, Stoddard JL, et al. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood. 2013 Apr 18. 121 (16):3117-25. [Medline].
Olbrich P, Lorenz M, Cura Daball P, Lucena JM, Rensing-Ehl A, Sanchez B, et al. Activated PI3Kδ syndrome type 2: Two patients, a novel mutation, and review of the literature. Pediatr Allergy Immunol. 2016 Sep. 27 (6):640-4. [Medline].
Alkhairy OK, Abolhassani H, Rezaei N, Fang M, Andersen KK, Chavoshzadeh Z, et al. Spectrum of Phenotypes Associated with Mutations in LRBA. J Clin Immunol. 2016 Jan. 36 (1):33-45. [Medline].
Schwab C, Gabrysch A, Olbrich P, et al. Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects. J Allergy Clin Immunol. 2018 Dec. 142 (6):1932-1946. [Medline].
Toubiana J, Okada S, Hiller J, et al. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood. 2016 Jun 23. 127 (25):3154-64. [Medline].
Nabhani S, Schipp C, Miskin H, et al. STAT3 gain-of-function mutations associated with autoimmune lymphoproliferative syndrome like disease deregulate lymphocyte apoptosis and can be targeted by BH3 mimetic compounds. Clin Immunol. 2017 Aug. 181:32-42. [Medline].
Fabre A, Marchal S, Barlogis V, Mari B, Barbry P, Rohrlich PS, et al. Clinical Aspects of STAT3 Gain-of-Function Germline Mutations: A Systematic Review. J Allergy Clin Immunol Pract. 2019 Jul - Aug. 7 (6):1958-1969.e9. [Medline].
Alsultan A, Basher E, Alqanatish J, Mohammed R, Alfadhel M. Deficiency of ADA2 mimicking autoimmune lymphoproliferative syndrome in the absence of livedo reticularis and vasculitis. Pediatr Blood Cancer. 2018 Apr. 65 (4):[Medline].
Barzaghi F, Minniti F, Mauro M, Bortoli M, Balter R, Bonetti E, et al. ALPS-Like Phenotype Caused by ADA2 Deficiency Rescued by Allogeneic Hematopoietic Stem Cell Transplantation. Front Immunol. 2018. 9:2767. [Medline].
Snow AL, Xiao W, Stinson JR, Lu W, Chaigne-Delalande B, Zheng L, et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J Exp Med. 2012 Nov 19. 209 (12):2247-61. [Medline].
Arjunaraja S, Angelus P, Su HC, Snow AL. Impaired Control of Epstein-Barr Virus Infection in B-Cell Expansion with NF-κB and T-Cell Anergy Disease. Front Immunol. 2018. 9:198. [Medline].
Nabhani S, Ginzel S, Miskin H, Revel-Vilk S, Harlev D, Fleckenstein B, et al. Deregulation of Fas ligand expression as a novel cause of autoimmune lymphoproliferative syndrome-like disease. Haematologica. 2015 Sep. 100 (9):1189-98. [Medline].
Li FY, Chaigne-Delalande B, Rao VK, Zhang Y, Matthews H, Kuijpers TT, et al. Clinical utility gene card for: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN). Eur J Hum Genet. 2015 Jun. 23 (6):[Medline].
Patiroglu T, Haluk Akar H, Gilmour K, Unal E, Akif Ozdemir M, Bibi S, et al. A case of XMEN syndrome presented with severe auto-immune disorders mimicking autoimmune lymphoproliferative disease. Clin Immunol. 2015 Jul. 159 (1):58-62. [Medline].
George LA, Teachey DT. Optimal Management of Autoimmune Lymphoproliferative Syndrome in Children. Paediatr Drugs. 2016 Aug. 18 (4):261-72. [Medline].
Rao VK, Straus SE. Causes and consequences of the autoimmune lymphoproliferative syndrome. Hematology. 2006 Feb. 11 (1):15-23. [Medline].
Li P, Huang P, Yang Y, Hao M, Peng H, Li F. Updated Understanding of Autoimmune Lymphoproliferative Syndrome (ALPS). Clin Rev Allergy Immunol. 2016 Feb. 50 (1):55-63. [Medline].
Caminha I, Fleisher TA, Hornung RL, Dale JK, Niemela JE, Price S, et al. Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome. J Allergy Clin Immunol. 2010 Apr. 125 (4):946-949.e6. [Medline].
Winter JN, Peterson LC. Lymphocytosis, lymphadenopathy: benign or malignant?. Hematology Am Soc Hematol Educ Program. 2015. 2015:106-10. [Medline].
Rao VK, Oliveira JB. How I treat autoimmune lymphoproliferative syndrome. Blood. 2011 Nov 24. 118 (22):5741-51. [Medline].
Miano M, Scalzone M, Perri K, Palmisani E, Caviglia I, Micalizzi C, et al. Mycophenolate mofetil and Sirolimus as second or further line treatment in children with chronic refractory Primitive or Secondary Autoimmune Cytopenias: a single centre experience. Br J Haematol. 2015 Oct. 171 (2):247-253. [Medline].
Völkl S, Rensing-Ehl A, Allgäuer A, et al. Hyperactive mTOR pathway promotes lymphoproliferation and abnormal differentiation in autoimmune lymphoproliferative syndrome. Blood. 2016 Jul 14. 128 (2):227-38. [Medline].
Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, et al. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7. 127 (1):17-28. [Medline].
Klemann C, Esquivel M, Magerus-Chatinet A, Lorenz MR, et al. Evolution of disease activity and biomarkers on and off rapamycin in 28 patients with autoimmune lymphoproliferative syndrome. Haematologica. 2017 Feb. 102 (2):e52-e56. [Medline].
Rao VK, Price S, Perkins K, Aldridge P, Tretler J, Davis J, et al. Use of rituximab for refractory cytopenias associated with autoimmune lymphoproliferative syndrome (ALPS). Pediatr Blood Cancer. 2009 Jul. 52 (7):847-52. [Medline].
Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ, et al. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop. Blood. 2010 Oct 7. 116 (14):e35-40. [Medline].

Media Gallery

Examples of an autoimmune lymphoproliferative syndrome (ALPS) in a patient with grade IV (visible) lymphadenopathy.
Autoimmune lymphoproliferative syndrome (ALPS) and ALPS-related disorders classification:
Primary and accessory diagnostic criteria for autoimmune lymphoproliferative syndrome (ALPS).
A patient with autoimmune lymphoproliferative syndrome (ALPS) who developed pneumococcal sepsis, a serious complication secondary to neutropenia and asplenia. Note the patient's cochlear implant; he has neurosensory hearing loss from prior episode of pneumococcal meningitis.
Positron emission tomography (PET) superimposed over a CT scan from a patient with autoimmune lymphoproliferative syndrome (ALPS). Note the massive cervical adenopathy. PET scans may be used as a screening tool in patients with autoimmune lymphoproliferative syndrome to decrease the number of lymph node biopsies used in screening for malignancy.
The extrinsic pathway of apoptosis. Mutations have been identified in each of the genes coding for Fas, Fas-ligand (FasL), caspase-8, and caspase-10. This figure was previously published in Rao VK, Straus SE. Autoimmune Lymphoproliferative Syndrome. Clinical Hematology. 58;759. 2006: Elsevier.
Suggested treatment algorithm for patients with autoimmune lymphoproliferative syndrome (ALPS). This schematic diagram is included only as a suggested guideline for managing children with autoimmune lymphoproliferative syndrome–associated autoimmune multilineage cytopenias. Use of granulocyte-colony stimulating factor (G-CSF) may be warranted for severe neutropenia associated with systemic infections. Similarly, use of other chemotherapeutic and immunosuppressive agents (eg, vincristine, methotrexate, mercaptopurine, azathioprine, cyclosporine, hydroxychloroquine, tacrolimus, sirolimus) besides mycophenolate mofetil (MMF) should be considered as a steroid-sparing measure or while avoiding or postponing surgical splenectomy at the discretion of the treating clinicians based on the circumstances of a specific patient.

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Author

Akaluck Thatayatikom, MD, RhMSUS Associate Professor, Pediatric Rheumatology Fellowship Training Program Director, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, University of Florida College of Medicine

Akaluck Thatayatikom, MD, RhMSUS is a member of the following medical societies: Allergy and Immunology Society of Thailand, American Academy of Allergy Asthma and Immunology, American College of Rheumatology, Childhood Arthritis and Rheumatology Research Alliance, Clinical Immunology Society, Medical Council of Thailand, Pediatric Society of Thailand, Royal College of Pediatricians of Thailand

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

Luke M Webb, MD Staff Physician, Department of Allergy and Immunology, Evans Army Community Hospital

Luke M Webb, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

David J Schwartz, MD Staff Physician, Department of Allergy and Immunology, Eisenhower Army Medical Center

David J Schwartz, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

V Koneti Rao, MD, FRCPA Staff Clinician, Lymphocyte Clinical Genomics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health

V Koneti Rao, MD, FRCPA is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Acknowledgements

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Acknowledgments

The authors acknowledge Drs Kip Hartman and Margaret Merino of the Pediatric Hematology and Oncology Department at the Walter Reed Army Medical Center for the use of their clinical expertise and patient photographs in this article. In addition, the authors thank Dr Scott Whitworth of the Department of Radiology at Walter Reed Army Medical Center for his assistance with positron emission tomography (PET) imaging. Finally, the authors also express thanks to the patients and parents who granted permission to use these photographs.

This research was supported by the Intramural Research Program of the National Institutes of Health. The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the US Government.

Which dietary modifications are used in the treatment of autoimmune lymphoproliferative syndrome (ALPS)?

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