Dermatologic Aspects of Addison Disease Clinical Presentation
- Author: Elizabeth A Liotta, MD; Chief Editor: William D James, MD more...
Symptoms are often nonspecific and include fatigue, weakness, anorexia, nausea, abdominal pain, gastroenteritis, diarrhea, and mood lability. Weakness and weight loss of 1-15 kg are universal features of Addison disease in the adults.
Nausea, vomiting, and diffuse abdominal pain are present in approximately 90% of patients and usually represent an impending addisonian crisis. Diarrhea is less common than nausea, vomiting, and abdominal pain and occurs in approximately 20% of patients. If diarrhea is present, it complicates the patient's already poor hydration status. Recurrent subtle flulike symptoms have been reported in few cases.
Mood disturbances include depression, irritability, and decreased concentration. Diagnosis may be delayed because of comorbid depression or other psychiatric illness.
Physical findings include hyperpigmentation of the skin and mucous membranes, decreased pubic and axillary hair in women, vitiligo, dehydration, and hypotension. Oral mucous membrane hyperpigmentation is pathognomonic for the disease.[3, 4]
Hyperpigmentation of the skin (see the images below) is considered a hallmark of Addison disease and is present in 95% of patients with chronic primary adrenal insufficiency. However, hyperpigmentation is not a universal sign of adrenal insufficiency. The presence of normal-appearing skin does not exclude the diagnosis.
The skin may appear normal, or vitiligo may be present. Increased pigmentation is prominent in areas of the skin that are subject to increased pressure, such as over the knuckles or the skin creases. Hyperpigmentation is also prominent on the nipples, axillae, perineum, and buccal mucosa (see the images below).
Longitudinal melanonychia has been reported as a presenting sign in rare cases.
Women may have loss of androgen-stimulated hair, such as pubic and axillary hair, because androgens are produced in the adrenal cortex. Men do not have hair loss because androgens in males are produced primarily in the testes.
Usually, systolic and diastolic blood pressures are reduced; the systolic blood pressure is lower than 110 mm Hg.
Insults to the adrenal glands are multifactorial and include autoimmune, infectious (eg, mycobacterial, fungal), neoplastic (eg, primary, metastatic), traumatic, iatrogenic (eg, surgery, medication), vascular (eg, hemorrhage, emboli, thrombus), and metabolic (eg, amyloidosis) events.
Most causes of Addison disease previously believed to be idiopathic are currently postulated to have an autoimmune etiology. Autoimmune destruction of the adrenal glands may be isolated or part of a multiorgan process. Isolated autoimmune insufficiency involves destruction of only the adrenal cortex, with no other organ involvement.
Polyglandular autoimmune diseases are primarily of 2 types: polyglandular autoimmune disease I (PGAD I) and polyglandular autoimmune disease II (PGAD II). PGAD I is described as destruction of the adrenal and thyroid glands resulting in adrenal insufficiency, hypothyroidism, and chronic candidiasis. PGAD I may also be associated with type 1 diabetes mellitus, hypogonadism, chronic hepatitis, immunoglobulin A (IgA) deficiency, chronic atopic dermatitis, keratoconjunctivitis, vitiligo, or alopecia. PGAD II, also called Schmidt syndrome, is characterized by autoimmune-mediated adrenal insufficiency and may involve autoimmune-mediated thyroiditis and/or autoimmune-mediated type 1 diabetes mellitus.
Autoimmune diseases begin with a genetic predisposition and then are triggered by an environmental agent. The active autoimmune process ensues, resulting in the metabolic abnormalities and physical symptoms of the disease. One half of 1% of type 1 diabetes mellitus patients are found to have Addison disease.
Antibodies to the adrenal cortex mediate autoimmune destruction of the adrenal glands. Three ACAs have been described: Antibodies to steroid 21-hydroxylase (21-OH) are the most common and specific for autoimmune adrenal destruction. Antibodies to steroid 17-hydroxylase (17-OH) and cytochrome P-450 (P-450 side chain–cleaving [P-450SCC] antibodies) are not as specific as antibodies to 21-OH because they are found in other tissues. (Steroid 17-OH is found in the gonads, and P-450MSCC, in the gonads and the placenta.) The expression of ACAs in patients without symptoms of Addison disease represents a significant risk of progression to adrenal insufficiency. The risk varies with age; children have a high risk of progression compared with adults, in whom the expression of ACAs represents a 30% risk of progression to Addison disease.
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