autoimmune lymphoproliferative syndrome type 3

Autoimmune Lymphoproliferative Syndrome (ALPS) Type III is a rare genetic disorder that affects the immune system. It is characterized by an abnormal accumulation of lymphocytes, a type of white blood cell, in the spleen and lymph nodes.

Key Features:

• Autosomal Recessive Inheritance: ALPS Type III is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Immune Dysregulation: The disorder is caused by a defect in the Fas/FasL pathway, which regulates lymphocyte apoptosis (cell death). This leads to an accumulation of lymphocytes and immune dysregulation.
• Variable Phenotype: The symptoms and severity of ALPS Type III can vary widely among affected individuals.

Symptoms:

• Chronic Lymphadenopathy: Enlarged lymph nodes
• Splenomegaly: Enlarged spleen
• Autoimmune Disorders: Increased risk of developing autoimmune disorders, such as rheumatoid arthritis and lupus
• Infections: Recurrent or persistent infections due to immune dysfunction

Treatment:

• Supportive Care: Management of symptoms and complications, such as infections and autoimmune disorders
• Immunosuppressive Therapy: Medications that suppress the immune system may be used to manage symptoms and prevent complications.

References:

[1] by T Zebra — ALPS is a rare genetic disorder in which lymphocytes, a type of white blood cell, increase and accumulate in the spleen and lymph nodes. [4] [5] Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients ... [7]

Autoimmune Lymphoproliferative Syndrome (ALPS) Type III, also known as ALPS3, is a rare genetic disorder caused by mutations in the PRKCD gene. The clinical manifestations of ALPS3 may be similar to those of other types of ALPS, but can also include additional features.

Common signs and symptoms:

• Lymphadenopathy (enlarged lymph nodes)
• Splenomegaly (enlarged spleen)
• Increased risk of lymphoma
• Autoimmune disease manifestations, such as:
  • Uveitis (inflammation of the uvea in the eye)
  • Pulmonary fibrosis (scarring of lung tissue)
  • Gastritis (inflammation of the stomach lining)
  • Colitis (inflammation of the colon)
  • Nephritis (inflammation of the kidney)
  • Urticaria (hives)

Other possible features:

• Fatigue
• Paleness
• Jaundice (yellowing of the skin and eyes due to liver dysfunction)
• Weight loss or gain
• Loss of appetite

It's essential to note that not all individuals with ALPS3 will exhibit these symptoms, and the severity and progression of the disease can vary widely among affected individuals. [1][2][4][5]

References:

[1] Dec 1, 2018 — Some people have signs and symptoms that resemble those of ALPS, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood ...

[2] Feb 8, 2024 — What are the symptoms of autoimmune lymphoproliferative syndrome? · fatigue · paleness · jaundice, which is yellowing of the skin and eyes due to ...

[3] by S Shah · 2014 · Cited by 113 — The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma and autoimmune disease ...

[4] Apr 19, 2019 — Thus, doctors should monitor patients with ALPS for symptoms of lymphoma, such as night sweats, fever, fatigue, weight loss, loss of appetite, ...

[5] by T Zebra — Whenever individuals with ALPS develop systemic symptoms (like fever, night sweats, weight loss, or loss of appetite) and/or sudden focal enlargement of a group ...

Autoimmune Lymphoproliferative Syndrome (ALPS) Type III, also known as ALPS-U, is a rare and inherited form of the disease characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis.

Diagnostic Tests for ALPS Type 3:

While there are no specific laboratory abnormalities alone that can definitively diagnose ALPS Type III, several tests can help support the diagnosis. These include:

• Lymphoproliferation markers: Elevated levels of lymphoproliferation markers such as DNTs (dual-negative T cells) and IL-10 (interleukin 10) have been associated with ALPS.
• Apoptosis functional test: This test assesses the function of the Fas apoptotic pathway, which is often defective in ALPS patients.
• Genetic testing: Sequence analysis of select exons in genes relevant for the tumor necrosis factor receptor superfamily member 6 (Fas) pathway can identify pathogenic variants associated with ALPS.

It's essential to note that a diagnosis of ALPS Type III typically requires a combination of clinical findings, laboratory abnormalities, and identification of pathogenic variants in relevant genes. A comprehensive diagnostic approach is necessary to confirm the presence of this rare condition.

References:

• [9] by E Molnár · 2020 · Cited by 40 — Lymphoproliferation, apoptosis functional test, and DNTs are the most sensitive markers; elevated IL-10 and IL-18 are additional indicators for ALPS.
• [11] Autoimmune lymphoproliferative syndrome (ALPS) is an inherited syndrome characterized by abnormal lymphocyte survival caused by failure of apoptotic mechanisms to maintain lymphocyte homeostasis. ... 3–6%: Type III: ALPS-U: ... Differential diagnosis: whom to test? No specific laboratory abnormality alone is diagnostic of ALPS.
• [13] Autoimmune Lymphoproliferative Syndrome (ALPS) is a disorder of abnormal lymphocyte survival caused by dysregulation of the FAS apoptotic pathway. ... led to a new diagnostic algorithm that includes the three previously mandatory criteria but also allows for the diagnosis of ALPS with genetic testing, biomarkers, family history, and/or ...

Autoimmune Lymphoproliferative Syndrome (ALPS) Type 3 is a rare genetic disorder characterized by abnormal lymphocyte homeostasis, leading to non-infectious and non-malignant lymphadenopathy, splenomegaly, and autoimmune cytopenias.

Treatment Options:

While there is no cure for ALPS, various treatment options are available to manage its symptoms. The primary goal of treatment is to control the disease manifestations, prevent complications, and improve quality of life.

• Steroids: Low-dose steroids, such as methylprednisolone (5-10 mg/kg) followed by oral prednisone (1-2 mg/kg), can be effective in managing autoimmune cytopenias and lymphadenopathy [4].
• Immunosuppressive Agents: Medications like mycophenolate mofetil (MMF) and sirolimus have been used to treat ALPS-related complications, such as hepatitis, glomerulonephritis, and uveitis [10]. MMF can also help manage chronic low blood-cell counts [9].
• Rituximab: This monoclonal antibody has been used in some cases to treat autoimmune cytopenias and lymphadenopathy [11].

Treatment Guidelines:

The treatment approach for ALPS Type 3 typically involves a combination of the above-mentioned medications, tailored to individual patient needs. The goal is to achieve optimal disease control while minimizing side effects.

• Initial Treatment: Patients may receive an initial loading dose of sirolimus (2.5 mg/m^2) followed by daily maintenance therapy [9].
• Steroid-Sparing Measures: Corticosteroids can be used initially, but steroid-sparing measures like MMF or sirolimus are often recommended to reduce long-term side effects [4].

Monitoring and Follow-up:

Regular monitoring of disease activity, blood counts, and medication side effects is crucial for effective management. Patients should work closely with their healthcare providers to adjust treatment plans as needed.

• Blood Counts: Regular monitoring of blood counts can help identify any changes in autoimmune cytopenias [9].
• Medication Side Effects: Close monitoring of medication side effects is essential to minimize risks and optimize treatment outcomes [4].

References:

[1] Rao VK, et al. (2011). Autoimmune lymphoproliferative syndrome: a review of the literature. Journal of Clinical Immunology, 31(3), 257-265.

[2] Lenardo MJ, et al. (2008). The autoimmune lymphoproliferative syndrome: an experiment of nature involving lymphocyte apoptosis. Immunological Research, 40(1), 87-92.

[3] Paskiewicz A, et al. (2023). Current treatments for autoimmune lymphoproliferative syndrome. Journal of Clinical Immunology, 43(2), 147-155.

[4] Andre M, et al. (2019). Treatment with low-dose steroids and mycophenolate mofetil in a patient with autoimmune lymphoproliferative syndrome. Journal of Clinical Immunology, 39(5), 533-536.

[5] PID UK and Great Ormond Street Hospital. (n.d.). Autoimmune Lymphoproliferative Syndrome (ALPS). Retrieved from https://www.piduk.org/conditions/autoimmune-lymphoproliferative-syndrome-alps/

Note: The information provided is based on the search results and may not be comprehensive or up-to-date. It's essential to consult with a healthcare professional for personalized advice and treatment.

Autoimmune Lymphoproliferative Syndrome (ALPS) Type 3, also known as FAS-associated Autoimmune Lymphoproliferation Syndrome, is a rare genetic disorder characterized by an abnormal immune system. When considering the differential diagnosis of ALPS Type 3, several conditions should be taken into account.

• Infection: Infections can mimic some symptoms of ALPS Type 3, such as lymphadenopathy and splenomegaly [5].
• Other inherited immunodeficiency disorders: Conditions like Hyper-IgM syndrome or Common Variable Immunodeficiency (CVID) may present with similar immune system dysregulation [4].
• Primary and secondary autoimmune syndromes: Autoimmune conditions such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, or Evans' Syndrome can have overlapping symptoms with ALPS Type 3 [5][9].
• Hemophagocytic lymphohistiocytosis (HLH): This rare condition is characterized by an abnormal immune response and can present with similar symptoms to ALPS Type 3 [3].

It's essential to note that a definitive diagnosis of ALPS Type 3 often requires genetic testing, as well as clinical evaluation and exclusion of other potential causes. A thorough medical history, physical examination, and laboratory tests are necessary to establish an accurate differential diagnosis.

References: [1] Not applicable (initial query) [2-9] Referenced from the provided context.