What are the symptoms of Autoimmune Lymphoproliferative Disease (ALPD)?

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Last updated: March 5, 2025View editorial policy

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From the Guidelines

Autoimmune Lymphoproliferative Disease (ALPD) typically presents with symptoms including lymphadenopathy, splenomegaly, and elevated TCR-DNT cells, as well as autoimmune cytopenias, polyclonal hypergammaglobulinemia, and a family history compatible with ALPS 1. The symptoms of ALPD can be divided into required and accessory criteria, with the required criteria including the presence of lymphadenopathy and/or splenomegaly, and elevated TCR-DNT cells 1. Some key points about the symptoms of ALPD include:

  • Lymphadenopathy must be persistent for more than 6 months and affect at least 2 nodal chains if isolated, with neoplastic and infectious causes excluded 1
  • Elevated TCR-DNT cells are a hallmark of the disease and must be distinguished from other cell types through costaining with TCR-directed antibodies 1
  • Accessory criteria include abnormal lymphocyte apoptosis assay, pathogenic mutations in genes of the FAS pathway, elevated circulating biomarkers, characteristic histopathology, autoimmune cytopenias, polyclonal hypergammaglobulinemia, and family history compatible with ALPS 1
  • Patients with ALPD may also experience symptoms such as fatigue, fever, joint pain and swelling, skin rashes, muscle weakness, and unexplained weight loss, although these are not specific to the disease 1 The diagnosis of ALPD is based on a combination of clinical and laboratory findings, and a definitive diagnosis requires the presence of both required criteria and at least one primary accessory criterion 1. In terms of specific symptoms, patients with ALPD may experience:
  • Lymphadenopathy, which can fluctuate and involve multiple nodal chains, including cervical, axillary, and inguinal chains 1
  • Splenomegaly, which can be associated with hepatomegaly in some cases 1
  • Autoimmune cytopenias, which can lead to anemia, low white blood cell counts, or low platelet counts 1
  • Polyclonal hypergammaglobulinemia, which can increase the risk of infections and other complications 1 Overall, the symptoms of ALPD can vary widely between individuals, and a comprehensive evaluation by specialists is necessary to establish a definitive diagnosis and develop an effective treatment plan 1.

From the Research

Symptoms of Autoimmune Lymphoproliferative Disease (ALPD)

The symptoms of Autoimmune Lymphoproliferative Disease (ALPD) include:

  • Noninfectious and nonmalignant lymphadenopathy 2, 3
  • Splenomegaly 2, 3, 4, 5
  • Autoimmune pathology, most commonly autoimmune cytopenias 2, 3, 6, 4
  • Autoimmune hemolytic anemia 3, 6, 5
  • Immune-mediated thrombocytopenia 3, 6, 5
  • Autoimmune neutropenia 3, 6
  • Hepatosplenomegaly 3, 5
  • Lymphadenitis with paracortical hyperplasia 5
  • Fever 5
  • Massive enlargement of the lymphoid organs 5
  • Predisposition to develop lymphoid malignancies, including Hodgkin and non-Hodgkin lymphoma 3, 4

Autoimmune Cytopenias

Autoimmune cytopenias associated with ALPS can result from:

  • Splenic sequestration 3
  • Autoimmune complications, including autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia 3, 6

Diagnosis and Treatment

Diagnosis of ALPS is based on clinical manifestations, laboratory tests, and genetic analysis 2, 3, 5. Treatment options include:

  • Corticosteroids 2, 5
  • Sirolimus and mycophenolate mofetil as corticosteroid-sparing therapies 2
  • Splenectomy in some cases 6, 4
  • Ongoing immunosuppressive treatment 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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