Autoimmune polyglandular syndrome type 1

The following disorders, which are components of APS-1, can also occur on their own, separate from the diagnosis? of APS-1:

Chronic? mucocutaneous candidiasis (CMC) refers to a condition of persistent or recurrent yeast infections of the skin, nails, and/or mucous membranes. The most prevalent of these organisms is Candida albicans. When significant CMC occurs, it is often a sign of an underlying T cell disorder, including APS-1. Fortunately, the conazole class of drugs has made this disease more easily managed than in former years. Candida is a yeast that is part of the normal flora of the gastrointestinal tract, skin, and mucous membranes. Healthy, intact skin and an intact immune system usually provide effective barriers to prevent candida from invading these tissues.

People with CMC present with recurrent or persistent candidiasis infections of the oral cavity (thrush) and other mucous membranes but often have more extensive involvement. The nails may be markedly thickened and discolored with significant swelling? of the surrounding tissue. The scalp may be involved, leading to alopecia in areas of scarring. However, alopecia is more commonly an autoimmune? disorder that can result in alopecia Universalis where all bodily hair is lost. There may be clinically significant esophageal candidiasis also in APS-1. Oropharyngeal cancers and cancers of the stomach and tongue occur at increased frequencies in APS-1. CMC is definitively diagnosed by the presence of Candida on fungal? skin scrapings.

Hypoparathyroidism is a condition characterized by insufficient production of parathyroid hormones by the parathyroid glands, the small, oval glands located behind the thyroid? gland in the neck. Parathyroid hormones (along with vitamin D) play a role in regulating levels of calcium in the blood. Due to a deficiency of parathyroid hormones, affected individuals exhibit abnormally low levels of calcium in the blood (hypocalcemia) often accompanied by elevated phosphorus.

Symptoms and findings associated with hypoparathyroidism may include weakness?, muscle cramps, excessive nervousness, headaches, and/or increased excitability (hyperexcitability) of nerves. This can lead to uncontrollable twitching and cramping spasms of certain muscles such as those of the hands, feet, arms, and/or face (tetany).

Hypoparathyroidism in APS-1 has an autoimmune? cause, but it can occur as a separate disorder associated with maldevelopment of the thymus, aortic arch, and parathyroid glands (DiGeorge syndrome) or may also arise as a separate inherited disorder. While an antibody to antigens present on the surface of parathyroid cells (the calcium-sensing receptor) had previously been reported in APS-1, more recently, researchers from University Hospital in Uppsala, Sweden have isolated another auto-antigen involved.

Chronic? adrenocortical insufficiency (Addison’s disease) is a rare disorder characterized by chronic, usually progressive, inadequate production of the steroid? hormones cortisol and aldosterone by the outer layer of cells of the adrenal glands (adrenal cortex). Classical Addison’s disease is a consequence of the loss of both of these hormones.

Cortisol affects carbohydrate metabolism, connective tissue development, arterial tone, and the amount of water in the body. The level of cortisol rises in response to physical and emotional stresses. Aldosterone affects the sodium (retention) and potassium (excretion) equilibria in the body. When these hormone levels are subnormal, blood pressure and blood volume drop due to increased excretion of salt and thereby water. Dehydration? can occur. Major symptoms of Addison’s disease include fatigue?, weakness?, gastrointestinal discomfort, salt craving, and changes in skin color (hyperpigmentation). Electrolyte disturbances include elevations in serum potassium and low serum sodium levels. Adrenal autoimmunity is associated with autoantibodies against an adrenocortical enzyme named 21-hydroxylase.

An acute?, life-threatening state of extreme insufficiency of adrenocortical hormones (Addisonian crisis) may occur in the form of a sudden loss of strength, dehydration?, and faintness from hypotension?. Females with APS-1 usually develop significant ovarian failures associated with autoantibodies against the side-chain cleavage and 17 alpha-hydroxylase enzymes of the ovaries. Hypogonadism is common and infertility is usually present.

Additional concerns with APS-1:

Autoimmunities can also involve the anterior pituitary gland (hypophysitis), the gastric mucosa (antibodies seen include parietal cell antibodies (antibodies against the hydrogen-potassium ATPase enzyme), and intrinsic factor binding proteins), celiac disease (antibodies against tissue transglutaminase enzyme of the intestinal mucosa), inflammatory bowel disease with autoimmunity directed at the serotonin rich cells of the small intestine (antibodies against the tryptophan hydroxylase enzyme), and interferons as mentioned above. Many patients are born with hypoplastic spleens, leaving them subject to septicemia, especially by strep pneumonia bacteria. It is advised that APS-1 patients be vaccinated against pneumococcus. The predisposition to GI cancers, especially involving the tongue and/or stomach, was also mentioned above.