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Dermatologic Aspects of Addison Disease Clinical Presentation

  • Author: Elizabeth A Liotta, MD; Chief Editor: William D James, MD  more...
 
Updated: Oct 08, 2015
 

History

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.[1]

Mood disturbances include depression, irritability, and decreased concentration. Diagnosis may be delayed because of comorbid depression or other psychiatric illness.

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Physical

Physical findings include hyperpigmentation of the skin[2] 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.

Hyperpigmented scar on diffusely hyperpigmented (t Hyperpigmented scar on diffusely hyperpigmented (tanned) skin. Courtesy of Dirk M. Elston, MD.
Hyperpigmented scars from ear piercing. Courtesy o Hyperpigmented scars from ear piercing. Courtesy of Dirk M. Elston, MD.

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).

Pigmented patches of mucous membrane and pigmented Pigmented patches of mucous membrane and pigmented longitudinal nail bands. Courtesy of Dirk M. Elston, MD.
Hyperpigmented gingival patches. Courtesy of Dirk Hyperpigmented gingival patches. Courtesy of Dirk M. Elston, MD.

Longitudinal melanonychia has been reported as a presenting sign in rare cases.[5]

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.

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Causes

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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Contributor Information and Disclosures
Author

Elizabeth A Liotta, MD Chief Dermatologist and Sole Proprietor, Integrated Skin Care Centers

Elizabeth A Liotta, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Alexander Brough, MD Consulting Surgeon, Department of Dermatology, Sewell's Point Clinic

Alexander Brough, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael J Wells, MD, FAAD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Robin Travers, MD Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians

Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Women's Dermatologic Society, Medical Dermatology Society

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Dr. Quenby Erickson, to the development and writing of this article.

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Hyperpigmented scar on diffusely hyperpigmented (tanned) skin. Courtesy of Dirk M. Elston, MD.
Hyperpigmented scars from ear piercing. Courtesy of Dirk M. Elston, MD.
Pigmented patches of mucous membrane and pigmented longitudinal nail bands. Courtesy of Dirk M. Elston, MD.
Hyperpigmented gingival patches. Courtesy of Dirk M. Elston, MD.
 
 
 
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