Treatment should be initiated promptly once the diagnosis has been made.
The optimal duration of treatment is not known; controlled data are limited.
As a general rule, a prolonged course of treatment should be expected.
Folic acid should be given for at least 3 months and up to 1 year depending on clinical response.
Antibiotic treatment has been given for periods between 2 weeks and 1 year, but most experience shows good outcomes with 3 to 6 months of treatment.
Vitamin B12 supplementation is also recommended if symptoms last more than 4 months or in the presence of low vitamin B12 levels, regardless of symptom duration.
Pathology
Tropical sprue (TS) causes mucosal changes throughout the digestive tract.
Histopathological analysis shows:
Marked villous atrophy of small bowel
Decrease in total absorptive surface area
Decreased absorption of long-chain fatty acids causes steatorrhea
Decreased protein absorption
Protein loss through the leaky mucosal membrane
Gastrointestinal stromal tumors
KIT gene mutation
PDGFRA mutation
Wild type (absence of KIT/PDGFRA)
Exon 9,13 & 17
Exon 11
Mutant succinate dehydrogenase
Uncontrolled KIT signalling
KIT receptor mutation
Dysfunction of electron transport mitochondria
Defective oxidative phosphorylation
Abnormal stabilization of HIF
Classification of pain in the abdomen based on etiology
tryptophan hydroxylase presenting with malabsorption
Tyrosine hydroxylase presenting with alopecia areata
Liver presenting with autoimmune liver disease and chronic active hepatitis
Steroidal hormone–producing cell presenting with hypogonadism.
X linked polyendocrinopathy, immune dysfunction and diarrhea. This condition is very rare and generally presents in neonatal period with diabetes and malabsorption. Unlike type 1 and type 2 autoimmune polyglandular syndromes there is no association with HLA genotype. Mutation in FOXP3 gene is inherited as X linked and leads to loss of regulatory T cells and autoimmunity.
The term “polyendocrine” itself is a misnomer, in that not all patients have multiple endocrine disorders, and many have nonendocrine autoimmune diseases. Nevertheless, the recognition that patients in whom multiple autoimmune disorders are diagnosed may have a specific genetic syndrome, may be at increased risk for multiple autoimmune disorders, and may have relatives who have an increased risk should spur clinicians toward early diagnosis and treatment.
In the simplest hypothesis for understanding organ-specific autoimmunity, the initial step is the loss of immunologic tolerance to a peptide within a specific molecule found in the target organ. Clones of the CD4 T cells that recognize the peptide then expand, and the specific cytokines produced by the clonal CD4 T cells favor inflammation (as when type 1 helper T [Th1]–cell clones produce cytokines such as interferon-γ) or favor autoantibody-mediated disease (as is the case predominantly with type 2 helper T [Th2]–cell clones).9 The probability of T-cell autoreactivity is determined both in the thymus (the site of central tolerance) and in the periphery (the site of peripheral tolerance) and is strongly influenced by specific HLA alleles
TYPE 1 APS
Mutations in the AIRE gene cause many autoimmune diseases, and affected patients are at risk for the development of multiple additional autoimmune diseases over time, including type 1A diabetes, hypothyroidism, pernicious anemia, alopecia, vitiligo, hepatitis, ovarian atrophy, and keratitis. Affected patients may also have diarrhea or obstipation that may be related to the destruction of gastrointestinal endocrine cells (enterochromaffin and enterochromaffin-like cells).39 Knockout of the AIRE gene in the mouse produces widespread autoimmunity, but the phenotype is relatively mild.
SYMPTOMS TYPE1 Addison's disease develops in 80 percent of patients with autoimmune polyendocrine syndrome type I, and type 1A diabetes develops in 18 percent
PROGNOSISI TYPE 1
After diagnosis, patients with autoimmune polyendocrine syndrome type I require close monitoring. Monitoring can help prevent illness associated with delayed diagnosis of additional autoimmune diseases (e.g., Addison's disease and hypoparathyroidism, which can develop during adulthood) as well as oral cancer, which may develop if candidiasis is not treated aggressively, and infection due to asplenism, which is present in a subgroup of patients.
In patients with autoimmune polyendocrine syndromes who have a single disorder such as Addison's disease or type 1A diabetes, the prevalence of additional autoimmune disorders is 30 to 50 times that in the general population.60,61 The concurrence of more than one endocrinopathy presumably results from shared genetic susceptibility leading to loss of tolerance to multiple tissues
TYPE 2
Autoimmune polyendocrine syndrome type II (also called Schmidt's syndrome with Addison's disease plus hypothyroidism) is much more common and more varied in its manifestations than autoimmune polyendocrine syndrome type I.
TYpe 3
X-Linked Polyendocrinopathy, Immune Dysfunction, and Diarrhea. The syndrome of X-linked polyendocrinopathy, immune dysfunction, and diarrhea (known as XPID) is an extremely rare disorder characterized by fulminant, widespread autoimmunity and type 1A diabetes, which usually develops in neonates; it is often fatal. The disorder is also known as XLAAD (X-linked autoimmunity and allergic dysregulation) and IPEX (immune dysfunction, polyendocrinopathy, and enteropathy, X-linked)
Aldosterone Deficiency:
Hyporeninemic hypoaldosteronism - Commonly seen in patients with renal insufficiency (diabetic kidney disease, chronic tubulointerstitial disease, or glomerulonephritis) and those that take certain medications (non-steroidal anti-inflammatory drugs, calcineurin inhibitors).[1]
Angiotensin inhibitors - angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), direct renin inhibitors
Heparin therapy (including low molecular weight heparin) - Heparin has a direct toxic effect on the adrenal zona glomerulosa cells which leads to a reduction in plasma aldosterone concentration.[9]
Primary adrenal insufficiency (Addison’s disease) - Associated with the lack of cortisol and aldosterone. This can result from autoimmune adrenalitis, infectious adrenalitis, and other disorders.[14]
Critical illness - There is decreased adrenal production of aldosterone and stress-induced hypersecretion of ACTH which can diminish aldosterone synthesis by diverting substrate to the production of cortisol.
Congenital isolated hypoaldosteronism - Deficiency of enzymes required for aldosterone synthesis.[14]
Pseudohypoaldosteronism type 2 (Gordon’s syndrome or familial hyperkalemic hypertension) - Abnormalities in WNK kinases in the distal nephron increase chloride reabsorption leading to reduced renal potassium secretion. Characterized by hypertension, hyperkalemia, metabolic acidosis, normal renal function, and low or low-normal plasma renin activity and aldosterone concentrations.[14][2]
Aldosterone Resistance:
Inhibitors of the epithelial sodium channel - Most commonly associated with the administation of potassium-sparing diuretics (spironolactone, eplerenone, amiloride) and certain antibiotics (trimethoprim, pentamidine).
Pseudohypoaldosteronism type 1 - Characterized by marked elevations of plasma aldosterone levels. There is an autosomal recessive form, and an autosomal dominant or sporadic form. The autosomal dominant form tends to be associated with milder symptoms
Type of
Adrenal insufficiency
Skin Pigmentation
ACTH
Normal ACTH
Addison disease
+
>60 ng/mL
5-30 ng/mL
Secondary /
tertiary adrenal insufficiency
-
<5 ng/mL
Addison's disease must be differentiated from other diseases that cause hypotension, skin pigmentation, and abdominal pain such as myopathies, celiac disease, Peutz-Jeghers syndrome ,anorexia nervosa, syndrome of inappropriate anti-diuretic hormone (SIADH), neurofibromatosis, porphyria cutanea tarda, salt-depletion nephritis and bronchogenic carcinoma.[7][8]
↑Morin L, Cargill YM, Glanc P (2016). "Ultrasound Evaluation of First Trimester Complications of Pregnancy". J Obstet Gynaecol Can. 38 (10): 982–988. doi:10.1016/j.jogc.2016.06.001. PMID27720100.
↑Balthazar EJ, Birnbaum BA, Yee J, Megibow AJ, Roshkow J, Gray C (1994). "Acute appendicitis: CT and US correlation in 100 patients". Radiology. 190 (1): 31–5. doi:10.1148/radiology.190.1.8259423. PMID8259423.
↑Bottomley C, Bourne T (2009). "Diagnosis and management of ovarian cyst accidents". Best Pract Res Clin Obstet Gynaecol. 23 (5): 711–24. doi:10.1016/j.bpobgyn.2009.02.001. PMID19299205.
↑ 4.04.14.2Bhavsar AK, Gelner EJ, Shorma T (2016). "Common Questions About the Evaluation of Acute Pelvic Pain". Am Fam Physician. 93 (1): 41–8. PMID26760839.
↑{{Cite journal
| author = W. E. Stamm
| title = Etiology and management of the acute urethral syndrome
| journal = Sexually transmitted diseases
| volume = 8
| issue = 3
| pages = 235–238
| year = 1981
| month = July-September
| pmid = 7292216
↑Selva-O'Callaghan A, Labrador-Horrillo M, Gallardo E, Herruzo A, Grau-Junyent JM, Vilardell-Tarres M (2006). "Muscle inflammation, autoimmune Addison's disease and sarcoidosis in a patient with dysferlin deficiency". Neuromuscul. Disord. 16 (3): 208–9. doi:10.1016/j.nmd.2006.01.005. PMID16483775.
