Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX) 

Updated: Aug 06, 2019
Author: Taylor Banks, MD; Chief Editor: Harumi Jyonouchi, MD 

Overview

Background

Immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a lethal syndrome first described as a unique entity by Powell et al in 1982.[1] It most commonly manifests with early onset, insulin-dependent diabetes mellitus; severe watery diarrhea, often with accompanying failure to thrive; and dermatitis. Other clinical features are more variable in their expression.[1, 2, 3]

Most affected children die within the first 2 years of life. IPEX syndrome is an X-linked recessive disorder with exclusive expression in males. The identification of mutations in the forkhead box protein 3 (FOXP3) gene associated with IPEX syndrome and a murine model has generated a considerable amount of interest and research.[2, 3] This has also extended into the therapeutic spectrum, with new immunosuppressive regimens and use of hematopoietic stem cell transplantation (HSCT).

Pathophysiology

IPEX syndrome is one of the monogenic autoimmune diseases, such as Wiskott-Aldrich syndrome and autoimmune lymphoproliferative syndrome (ALPS). A potential murine model was identified in mice suffering from Scurfy syndrome. Using information gathered from these mice, researchers mapped the forkhead box protein 3 (FOXP3) gene to Xp11.23-Xq13.3.[1, 2, 4] This is a genetic region also closely associated with the WASP gene responsible for Wiskott-Aldrich syndrome. The FOXP3 gene is part of a family of genes that are strongly associated with normal immune responses and thymic development.[5]

FOXP3 has recently been linked with the development of immunosuppressive CD4+ CD25+ regulatory T cells, which form in the thymus and represent a subset (5–10%) of the helper CD4+ T cells.[6] These cells have been noted in previous studies to dampen immune responses, including in the setting of autoimmune diseases.[7] When the FOXP3 gene is absent or dysfunctional, this specific subset of regulatory T-cells (Treg) fails to develop normally, though variable function has been noted in more recent studies.[8, 9] Although the role of Tregs in self-tolerance and immune homeostasis is of critical importance, the mechanism by which they exert these effects has not been fully elucidated.[5, 6]

More recent studies have uncovered links between FOXP3 dysfunction and an inflammatory helper T-cell subtype (Th17), as well as loss of peripheral B-cell tolerance.[10, 11] Ongoing research seeks to better characterize the full extent and implications of these and other manifestations of immune dysregulation.

Although patients with IPEX syndrome share many of the same core clinical and immune manifestations of the disease, the expressed phenotypes vary. Elevated immunoglobulin E (IgE) and immunoglobulin A (IgA) levels and eosinophilia have been noted but are not universally present in affected individuals. Neutrophil activity and complement levels are generally normal, although neutropenia has been reported.[6] Similarly, levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) can be normal but are often slightly depressed in older individuals, likely as a result of protein loss from their enteropathy.[2]

Other clinical effects are also variably present, with some patients demonstrating thrombocytopenia, lymphadenopathy, tubular nephropathy, hypothyroidism, and alopecia in addition to the more common triad of dermatitis, insulin-dependent diabetes, and enteropathy. Although not fully understood, the presence of diabetes appears to be related to inflammatory destruction of the islet cells, supported by the histologic presence of lymphocytic infiltrates of the pancreas.[3, 12] In terms of the enteropathy seen in IPEX syndrome, a celiac-like pattern with villous-blunting is noted along with a similar lymphocytic infiltrate.[13] The cutaneous manifestations are most often eczematous but can also take on a spongiotic psoriasiform appearance histologically.[14]

Epidemiology

Frequency

IPEX syndrome is a rare disorder that affects an estimated 1 in 1.6 million people.[15]

Fewer than 150 individuals have ever been diagnosed with immunodysregulation polyendocrinopathy enterology x-linked (IPEX) syndrome, but there may be many unreported cases.[16]

Mortality/Morbidity

Children who do not receive treatment usually die within the first 2 years of life. Sepsis and complications from failure to thrive are the most common causes of death.[6]

In those patients who developed sepsis, enterococcal, staphylococcal, and candidal species as well as cytomegalovirus were the most commonly identified infectious agents.[5] Enterococcal and staphylococcal species have also been predominant in complications of immunosuppressive treatment, including catheter-associated infections, peritonitis, pneumonitis, and septic arthritis.[3]

Hematopoietic stem cell transplantation (HSCT) is an option, and increased success has been noted with “reduced-intensity” conditioning protocols. However, HSCT in patients with IPEX syndrome has met with significant complications and death rates, which may be increased compared with patients undergoing the procedure for other conditions.[3, 6, 17]

Demographics

The disease manifests shortly after birth and, in most cases, in the first 3–4 months of life. Because the condition is rare, no large scale studies or reports have been completed to aid further delineation of the age-related characteristics of IPEX syndrome.[1, 6]

Only males have been noted to be affected in this X-linked recessive process. Obligate carrier females have all been healthy in cases reviewed in the literature. The female IPEX syndrome carriers do not appear to be subject to disease manifestation related to a skewed pattern of lyonization or inactivation of the unaffected X-chromosome.[3]

No difference in the incidence of IPEX syndrome among individuals of different races is known.

Prognosis

If untreated, death from complications of IPEX syndrome usually occurs within the first 2 years of life. Death is often attributable to metabolic abnormalities, malnutrition secondary to malabsorption, or severe sepsis.

The introduction of immunosuppressive treatments has improved survival in patients with IPEX syndrome. Successful hematopoietic stem cell transplantation (HSCT) with immune reconstitution has been reported and offers hope of a permanent cure.[6]

Patient Education

Educate patients and families about IPEX syndrome and associated infectious and autoimmune complications. Patients should be able to recognize signs of infection, diabetes, thyroid disease, enteropathy, anemia, thrombocytopenia, or neutropenia and seek medical care.

Female carriers should receive appropriate genetic counseling.

Patients with IPEX syndrome should receive nutritional counseling.

Patients with diabetes should receive appropriate diabetic instruction.

 

Presentation

History

Immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome should be considered in young male patients with intractable diarrhea with accompanying villous atrophy or failure to thrive. Further support for the diagnosis is gained by the presence of the other 2 elements of the predominant triad: eczematous or psoriasiform dermatitis and early onset, insulin-dependent diabetes.[5, 12]

Failure to thrive, growth retardation, and/or cachexia in the setting of watery, secretory diarrhea are common historical elements. The diarrhea is occasionally present prior to feeding but generally appears or worsens after feeds. Enteric rest and gluten-free diet do little to alter the course of the enteropathy.[3]

Glucose intolerance can present at birth, but generally the patients manifest symptoms after 3-4 months of life. Anti-islet cell antibodies have been found in some patients.[5]

Thyroid disease, both hyperthyroidism and hypothyroidism, has been noted in as many as 30% of patients; hypothyroidism is more common.[12]

The forms of dermatitis vary, with many patients presenting with an eczematous rash; however, a diffuse erythematous rash, psoriasiform rashes, pemphigoid nodularis, and, rarely, alopecia universalis have been noted.[5, 14]

One third of patients develop renal disease, with proteinuria and hematuria representing the most common presenting symptoms.[5]

A history of thrombocytopenia or Coombs test–positive anemia may also be present.[2]

Physical

Patients’ general appearance, growth, and development are important to note. Cachexia, small size, and poor weight gain related to failure to thrive are often present.[3]

Skin examination can detect the several possible forms of dermatitis, including eczematous, psoriasiform, and a more generalized erythematous rash and, rarely, alopecia universalis.[5, 14]

A joint examination may reveal signs of arthritis, such as edema, erythema, and limitation of range of motion, but joint involvement is not common.[12]

Lymphadenopathy and splenomegaly are variably present.[2]

Causes

The FOXP3 gene at Xp11.23-Xq13.3 is the causative gene for IPEX syndrome. This gene is critical for the development of CD4+ CD25+ regulatory T cells (Treg). The absence of these cells has been linked to autoimmune disease and other forms of immune dysregulation.

Of patients with IPEX syndrome, 60% have identifiable mutations in the FOXP3 gene. Some patients with IPEX-like conditions may have mutations involving the regulatory sequences in the FOXP3 gene.[18, 19] A growing understanding of related, IPEX-like conditions now includes mutations in CD25, STAT5b, and ITCH syndrome. These conditions also impact Treg cells or signaling pathways in which FOXP3 also participates.[20]

It is an X-linked recessive disease process, and a male child of a female carrier has a 50% chance of being affected. A female child has a 50% probability of being an asymptomatic carrier.

The phenotypic manifestations of this disease vary, and their relationship to the monogenic origin is unclear.

Complications

Complications include the following:

  • Infection

  • Malnutrition

  • Complications of the associated endocrine abnormalities

  • Complications of the associated hematologic abnormalities

  • Complications of hematopoietic stem cell transplantation (HSCT)

 

DDx

Differential Diagnoses

  • Autoimmune polyendocrinopathy syndrome (APS) type I

  • Autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED)

  • ITCH syndrome

  • Immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX)-like syndromes (CD25+ deficiency, STAT5b)

  • Omenn Syndrome

  • Pancreatic hypoplasia or agenesis

  • Pediatric Wiskott-Aldrich Syndrome

  • STAT1 (gain of function mutations)

  • Schmidt syndrome/APS type II

  • Transient neonatal diabetes

  • X-linked autoimmune enteropathy

  • X-linked thrombocytopenia

 

Workup

Laboratory Studies

Molecular genetic testing for immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome can be performed by DNA sequencing of the FOXP3 gene and mutation analysis.[21] Sixty percent of patients with IPEX syndrome have an identifiable mutation in FOXP3. Patients with IPEX-like conditions with no identifiable mutation in FOXP3 may have mutations in the regulatory sequences in the FOXP3 gene or in pathways related to regulatory T-cell development or function.[19, 20]

While genetic testing modalities remain the criterion standard, one paper does highlight autoantibody markers to harmonin and villin as a possible diagnostic tool for IPEX syndrome; however, more research is needed.[22, 23]

Although not diagnostic, other laboratory tests may support the diagnosis of IPEX syndrome.

Thyroid-stimulating hormone (TSH), FT4, and thyroid antibodies are used to evaluate for autoimmune thyroid disease.

Serum glucose test, oral glucose tolerance test, and anti-islet cell antibodies testing are used to assess insulin-dependent diabetes. Anti–glutamic acid decarboxylase (GAD) antibodies and anti-insulin antibodies have also been reported in patients with IPEX syndrome.[7]

CBC count with differential is used to evaluate for autoimmune hemolytic anemia, thrombocytopenia, and/or neutropenia. Marked eosinophilia has been described. If anemia is present, evaluation for autoantibody production with Coombs testing may be performed. Patients with IPEX syndrome usually have intermittent eosinophilia.[12, 24]

BUN and creatinine level measurement and urinalysis with microscopy is used to assess evidence of autoimmune renal disease.

Liver function tests assess for evidence of autoimmune liver disease.

Serum immunoglobulin E (IgE) and immunoglobulin A (IgA) levels are usually elevated in patients with IPEX syndrome.[12]

Flow cytometry of peripheral blood CD4+ CD25+ FOXP3+ usually reveals decreased T cells in patients with IPEX syndrome.[25]

Imaging Studies

Imaging studies are not routinely required for the diagnosis and management of IPEX syndrome.

Consider targeting imaging studies to evaluate for sinus disease and potential bronchiectasis.

Other Tests

Quantitative immunoglobulins (immunoglobulin G [IgG], immunoglobulin M [IgM], immunoglobulin A [IgA]), antibody response to protein and polysaccharide antigens, and B-cell subsets are normal. Low immunoglobulin levels in a patient with IPEX syndrome is suggestive of a significant protein-losing enteropathy.[12]

T-cell subsets, in vitro lymphocyte proliferative response to mitogens, and delayed-type hypersensitivity are normal. Increased TH-2 cytokine (interleukin [IL]-4, IL-5, IL-13) and decreased TH-1 cytokine (interferon [INF]-γ) expression has been reported in patients with IPEX syndrome.[14]

Although autoimmune neutropenia is commonly found in IPEX syndrome, neutrophil function is preserved.

Patients with IPEX syndrome have normal serum complement levels.[12]

Procedures

Endoscopy (upper and lower) with biopsy is used to evaluate for enteropathy. Skin biopsy is used to characterize dermatitis.

Histologic Findings

All 3 of the histologic findings below are associated with various degrees of villous atrophy and cellular inflammatory infiltrate.[13]

  • Graft versus host disease –like pattern associated with positive antienterocyte antibodies (most common)[13]

  • Celiac disease –like pattern[13]

Enteropathy with complete depletion of goblet cells was also associated with IPEX syndrome.[13]

Lymphocytic infiltrate with destruction of exocrine tissue and loss of islet cells is observed.[12]

Dermatologic findings include the following:[26]

  • Eczematous dermatitis

  • Psoriaform lesions

  • Lymphocytic dermal infiltrate

Thyroid findings include the following:

  • Lymphocytic infiltrate[12]

  • Thymus

  • Depletion of lymphocytes and Hassall corpuscles with cellular atrophy or dysplasia[12]

Staging

See the list below:

  • No current staging classification has been established for IPEX syndrome. However, emerging research may provide a basis for development of a staging system.[27]

 

Treatment

Medical Care

Hematopoietic stem cell transplantation (HSCT) and chronic immunosuppression represent the two main therapeutic interventions for immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. HSCT is the only curative treatment for IPEX[28] . Although conventional myeloablative conditioning has been associated with significant treatment-related mortality, emerging evidence suggests that reduced intensity conditioning holds promise as a treatment modality. Some more limited data have suggested a higher rate of graft failure, particularly when compared to other immune disorders, but more study is required. Early identification of IPEX and treatment via HSCT hold the potential to reduce the effects of chronic immunosuppressive regimens and disease-related organ damage.[29, 30, 31, 32]

Supportive therapies may be required for other disorders associated with IPEX syndrome, including the following:

  • Insulin-dependent diabetes mellitus: Insulin replacement is indicated.

  • Autoimmune thyroid disease: Hypothyroidism is treated with levothyroxine. Hyperthyroidism is treated with anti-thyroid medications, radioactive iodine131 I, or thyroidectomy.

  • Enteropathy: Immunosuppressive agents such as oral corticosteroids, cyclosporin A, tacrolimus, sirolimus, rituximab, and infliximab have been successful to control symptoms but fail to provide long-term remission.[6] Nutritional support is indicated.

  • Dermatitis: Emollients, topical steroids, and other anti-inflammatory agents are indicated.

  • Autoimmune cytopenias: Corticosteroids, granulocyte-colony stimulating factor (G-CSF, filgrastim) for neutropenia, and replacement blood products

  • Infections: Antibiotics are indicated.

A recent study by Passerini et al (2013) highlights the possibility of using adoptive cell therapy with genetically engineered regulatory T cells as a novel therapy for IPEX syndrome.[33, 34] More research is needed to explore this and related gene therapy approaches.

Consultations

Evaluation of the immune system should be performed through consultation with an immunologist.

Patients with IPEX syndrome should be referred to an endocrinologist for management of diabetes and thyroid disease.

Consultation with a gastroenterologist is indicated for diagnosis and management of enteropathy.

Patients with autoimmune cytopenias may benefit from consultation with a hematologist to assist with management.

Proper diagnosis and management of the skin manifestations associated with IPEX syndrome may require consultation with a dermatologist.

Nutrition consultation may be beneficial in patients with IPEX syndrome.

Patients with evidence of renal disease should be referred to a nephrologist for diagnosis and management.

Patients with recurrent and severe infections may benefit from consultation with an infectious disease specialist.

A transplant team should be consulted if hematopoietic stem cell transplantation (HSCT) is considered.

Patients and families with IPEX syndrome should be referred to a geneticist for evaluation and counseling.

Diet

Dietary management of IPEX syndrome varies according to the degree of enteropathy and response to treatment and may include the following:[35]

  • Regular diet

  • Low carbohydrate diet

  • Elemental formula

  • Total parenteral nutrition

Activity

Patients with thrombocytopenia should take precautions to prevent bleeding. Patients with severe anemia should avoid strenuous activity. Patients with diabetes should monitor their glucose while exercising to avoid hypoglycemia. Patients with uncontrolled hypothyroidism may have difficulty maintaining concentration and slowed reaction times. Activities with a high risk of injury should be avoided.

Prevention

Genetic testing and prenatal diagnosis may reduce the incidence of this condition. The possibility of prenatal diagnosis has been suggested by recent research.[36]

Early hematopoietic stem cell transplantation (HSCT) may prevent end-organ damage associated with this disease.

 

Medication

Medication Summary

Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome.[29, 30] However, numerous medications are used to treat the various disease associations.

Medications should be used on an individual basis with consideration of the particular disease targeted and individual response to therapy. Diabetes is treated with replacement insulin. Thyroid disease may be treated with either replacement thyroid hormone or antithyroid medications, depending on the underlying thyroid condition. Topical steroids and anti-inflammatory medications are used to treat the dermatitis associated with IPEX syndrome. Cytopenias can be treated with granulocyte-colony stimulating factor (G-CSF), corticosteroids, or replacement blood products in more severe cases. Infections associated with IPEX syndrome usually respond to antibiotics, antiviral, or antifungal therapy. These medications can be targeted against the specific pathogen, if known.

Immunosuppressive medications are the mainstay of treatment for the enteropathy associated with IPEX syndrome. Medications that have been reported to reduce GI symptoms include high-dose corticosteroids, cyclosporin A, tacrolimus, sirolimus, infliximab, and rituximab. None of these medications have demonstrated remission, although sirolimus has demonstrated sustained symptom reduction for as long as 5 years.[6] The side effects of these medications include infectious complications, risk of malignancy, and end-organ toxicity. Because IPEX syndrome is rare, no large-scale comparative studies of these medications have been performed, and optimal dosing has not been established.

Immunomodulators

Class Summary

These agents modify immune processes that promote inflammation, without causing generalized immunosuppression.

Rituximab (Rituxan)

Antibody genetically engineered. Chimeric murine/human monoclonal antibody directed against the CD20 antigen found on surface of B-lymphocytes. It eliminates circulating CD20+ B cells with resultant reduction of autoantibody production and B cell (as an antibody presenting cells) mediated immune activation.

Infliximab (Remicade)

Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-α and inhibits its binding to TNF-α receptor. Reduces infiltration of inflammatory cells and TNF-α production in inflamed areas. Used with methotrexate in patients that have had inadequate response to methotrexate monotherapy.

Immunosuppressant Agents

Class Summary

Selective inhibitors of T-cell lymphocytes (eg, cyclosporine) suppress early cellular response to antigenic and regulatory stimuli.

Traditionally, high-dose steroids were thought to be lympholytic, but recent studies have suggested that steroids may inhibit T-cell proliferation and T-cell–dependent gene expression of cytokines. They produce nonspecific anti-inflammatory effects and antiadhesion effects that contribute to immune suppression.

Cyclosporine (Gengraf, Neoral, Sandimmune)

An 11-amino acid cyclic peptide and natural product of fungi. Acts on T-cell replication and activity. Specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting T-cell function by blocking a Ca/calmodulin-NFAT mediated signaling pathway. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.

Binds to cyclophilin, an intracellular protein, which, in turn, prevents T-cell activation, transcription of T-cell cytokines, and the subsequent recruitment of activated T cells. Has about 30% bioavailability, but marked interindividual variability is noted. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that drug be present during first 24 h of antigenic exposure.

Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease) for various organs.

Tacrolimus (Prograf)

Immunomodulator produced by the bacteria Streptomyces tsukubaensis. Mechanisms of action similar to cyclosporine. Primarily used in transplants but used in Behçet disease to treat uveitis.

Sirolimus (Rapamune)

Inhibits lymphocyte proliferation by interfering with signal transduction pathways. Binds to immunophilin FKBP12 to block action of mTOR. FDA approved for prophylaxis of organ rejection in patients receiving allogeneic renal allografts.

Prednisone

Prednisone or other systemic corticosteroids elicit immunosuppression for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and also suppresses lymphocyte and antibody production.

 

Follow-up

Further Outpatient Care

Close medical follow-up and specialty care is required to monitor and manage the infections and autoimmune complications of IPEX syndrome.

Further Inpatient Care

Patients who have immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome and severe infections may require intravenous antimicrobial treatment.

Some immunosuppressive drugs may be only administered in an inpatient setting.

Diabetic patients presenting in diabetic ketoacidosis (DKA) may require inpatient monitoring of glucose in addition to fluid and electrolyte resuscitation.

Severe cytopenias may require treatment with intravenous steroids or blood products.

Severe malnutrition from enteropathy may require total parenteral nutrition.

Hospitalization for conditioning prior to hematopoietic stem cell transplantation (HSCT) may be required.

Transfer

Patients with IPEX syndrome may require transfer to a center that provides multiple subspecialty care.

Care may be obtained at a center that specializes in the diagnosis and treatment of IPEX syndrome.

Transfer to a center that performs hematopoietic stem cell transplantation (HSCT) may be indicated.

 

Questions & Answers

Overview

What is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the pathophysiology of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the prevalence of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the mortality and morbidity associated with immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

At what age does immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome typically present?

What are the sexual predilections of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What are the racial predilections of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the prognosis of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is included in patient education about immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Presentation

Which clinical history findings are characteristic of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Which physical findings are characteristic of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What causes immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What are the possible complications of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

DDX

What are the differential diagnoses for Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX)?

Workup

What is the role of lab tests in the workup of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the role of imaging studies in the workup of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the role of antibody testing in the workup of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

What is the role of endoscopy in the workup of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Which histologic findings are characteristic of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

How is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome staged?

Treatment

How is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome treated?

Which specialist consultations are beneficial to patients with immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Which dietary modifications are used in the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Which activity modifications are used in the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

How is immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome prevented?

What is the role of hematopoietic stem cell transplantation (HSCT) in the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Medications

What is the role of medications in the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

Which medications in the drug class Immunosuppressant Agents are used in the treatment of Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX)?

Which medications in the drug class Immunomodulators are used in the treatment of Immunodysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome (IPEX)?

Follow-up

What is included in the long-term monitoring of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

When is inpatient care indicated for the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?

When is patient transfer indicated for the treatment of immune dysfunction, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome?