Recurrent Oral Inflammation in Autoimmune Lymphoproliferative Syndrome

Malgorzata Pac, Dorota Olczak-Kowalczyk, Beata Wolska-Kuśnierz, Barbara Piątosa, Renata Górska, Ewa Bernatowska
4.524 1.185



Background and aim: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the Fas apoptotic pathway. In ALPS defective lymphocyte apoptosis manifests as a chronic, nonmalignant lymphadenopathy and/or splenomegaly/hepatosplenomegaly, expansion of double negative T cell (DNTC) – CD4-CD8-TCRαβ+ T cells, autoimmune cytopenias and other autoimmune diseases.  Patients demonstrate oral lesions which have not yet been reported in the literature.

The aim of the study was to present the oral status of children with ALPS, associated mainly with haematologic and immunologic disorders.

Material and methods: Among almost 1500 patients with primary immune deficiency diagnosed between 1980 and 2012 at the Department of Immunology, Children's Memorial Hospital, Warsaw (Poland) 7 cases of ALPS were identified according to ALPS diagnostic criteria. Routine immunological parameters were evaluated (serum immunoglobulin levels, immunophenotyping of peripheral lymphocytes, DNT cells, proliferative response to mitogens), vitamin B12 level, haematological and biochemical laboratory tests. Clinical course was retrieved retrospectively from medical records and evaluated during control visits. All patients were offered dental evaluation and treatment. Clinical examinations included the status of marginal gingiva, oral mucosa (the presence and type of lesions) and presence of caries.  

Results and conclusions: Almost all patients presented with leukopenia and granulocytopenia during control visits. Unsatisfactory oral hygiene status, carious cavities and gingivitis were found in all patients. In six subjects oral ulcers were also noticed.  In two of them gingivitis was assessed as severe (with redness, swelling and spontaneous gingival bleeding), in other - as mild. An association between hematological and immune disorders and the health status of the oral mucosa and gingivae was observed in all but one patient. Findings included pale oral mucosa, a smooth tongue, recurrent mucosal ulcers, and gingivitis with bleeding. Their onset was accompanied by deterioration in the patients' general health condition and the presence of local causative factors.

Recurrent oral inflammation/aphtae can be the first symptom of ALPS and should be taken into account in differential diagnosis by paediatrician or general practitioner. It indicates strong need for cooperation between the dentists and immunologists and haematologists.  



autoimmune lymphoproliferative syndrome, neutropenia, gingivitis, oral ulcers, dental caries

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Blessing JJH. Autoimmune lymphoproliferative syndrome. In: Stiehm ER, Ochs HD, Winkelstein JA, eds. Immunologic Disorders in Infants & Children, Philadelphia: Elsevier, 2004. pp. 6056

Bleesing JJ. Autoimmune lymphoproliferative syndrome (ALPS). Curr Pharm Des 2003; 9:265–

Speckmann C, Rohr J, Ehl S. Genetic Disorders of Immune Regulation. In: Rezaei N, Aghamohammadi A, Notarangelo LD, eds. Primary Immunodeficiency Diseases. Definition, Diagnosis, and Management, Berlin: SpringerVerlag Berlin Heidelberg, 2008. pp. 178-182.

Sneller MC, Dale JK, Straus SE. Autoimmune lymphoprolifertive syndrome. Curr Opin Rheumatol 2003; 15:417-21.

Infante AJ, Britton HA, DeNapoli T, Middelton LA, leonardo MJ, Jackson The clinical spectrum in a large kindred with autoimmune lymphoproliferative syndrome caused by a Fas mutation that impairs lymphocyte apoptosis. J Pediatr 1998; 133:629-33.

Lehman HK, Ballow M. Immune deficiency disorders with autoimmunity and abnormalities in immune regulation – monogenic autoimmune disorders. Clinic Rev Allerg Immunol 2008; 34:141-5.

John JM, Rajasekhar R, Mathews V. Autoimmune lymphoproliferative syndrome (ALPS): a rare cause of immune cytopenias, Indian Pediatr 2008; 45:148-50.

Campagnoli MF, Garbarni L, Quarello P, Garelli E, Carando A, Baravalle V et al. The broad spectrum of autoimmune lymphoproliferative disease: molecular bases, clinical features and long-term follow-up in 31 patients. Haematologica, 2006; 91:538-41.

Oliveira JB et al, Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop, Blood 2010, 116, 14, e30-e40

Rao VK, Oliveira JB,How I treat autoimmune lymphoproliferative syndrome, Blood 2011, 118, 5741-51

Hong YH, Lee CK. Autoimmune lymphoproliferative syndrome – like syndrome presented as lupus-like syndrome with mycobacterial joint infection evolved into the lymphoma. Rheumatol Int 2009; 29: 569-73.

Kossiva L, Theorodoridou M, Mostrou G, Vrachnou E, Deist LeF, Rieux-Laucat F et al. Mycophenolate mofetil as an alternate immunosuppressor for autoimmune lymphoproliferative syndrome, J Pediatr Hematol Oncol 2006; 28:824-6.

Löe H.: The Gingival Index, the Plaque Index. J. Periodontol., 1967; 38, 610-616

Atkinson J, O’Connell A, Aframian D. Oral manifestations of primary immunological diseases. J Am Dent Assoc 2000; 131:345-56.

Andrews T, Sullivan KE. Infections in patients with inherited defects in phagocytic function. CMR 2003; 16:597-621.

Olczak-Kowalczyk D, Matosek A, Wrześniewska D. Clinical expression of primary immunodeficiency disorder of oral mucosa. Standardy Med 2006; 4:447-53 [in Polish].

Antonio AG, da Costa Alcantara PC, Ramos MEB, de Souza IPR. The importance of dental care for a child with severe congenital neutropenia: a case report. Spec Care Dentist 2010; 30:261-65.

Rezaei N, Farhoudi A, Ramyar A, Pourpak Z, Aghamohammadi A, Mohammadpour B et al. Congenital neutropenia and primary immunodeficiency disorders: a survey of 26 Iranian patients. J Pediatr Hematol Oncol 2005; 27:351-6.

Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial. J Am Board Fam Med, 2009; 22:9–16.

Derossi SS., Garfunkel A, Greenberg M. Hematologic diseases. In: Burket LW, Greenberg MS, Glick M, eds. Burket's oral medicine: diagnosis & treatment, BC Decker, 2003. pp. 429 Socransky SS, Smith C, Haffajee AD. Subgingival microbial profiles in refractory periodontal disease. J Clin Periodontol 2002; 29:260-8.

Parahitiyawa NB, Jin LJ, Leung WK, Yam WC, Samaranayake LP. Microbiology of Odontogenic Bacteremia: beyond Endocarditis. Clin Microbiol Rev 2009; 22:46-64.

Parahitiyawa, N. Scully, C. Leung, W. Yam, W. Jin, L. Samaranayake, L. Exploring the oral bacterial flora: current status and future directions Oral Diseases 2010 16, 136-145

Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the Normal Bacterial Flora of the Oral Cavity. J Clin Microbiol 2005; 43:5721-32.

Smolewska E: The significance of infections in autoimmune diseases. Reumatol 2009; 47: 332–8 [In Polish].

Burke JS. Waldeyer’s ring, sinonasal region, salivary gland, thyroid gland, central nervous system, and other extranodal lymphomas and lymphoid hyperplasias. In: Knowles DM, eds., Neoplastic hematopathology, Philadelphia: Lippincott Williams & Willkins, 2001. pp. 1351–

Ferry JA, Harris NL: Lymphomas and lymphoid hyperplasia in head and neck sites. In: Pilch BZ, eds. Head and neck surgical pathology, Philadelphia: Lippincott Williams and Wilkins, 200 pp. 476–533. Yin HF, Jamlikhanova V, Okada N, Takagi M. Primary natural killer/T-cell lymphomas of the oral cavity are aggressive neoplasms. Virchows Archiv 1999; 435:400-6.