David Adelson MD
Christine Ahn MD
Sanah Ali MD
Carl Allen DDS, MSD
Brandon Ayres MD
Howard P. Baden MD
Yevgeniy Balagula MD
Robert Baran MD
Keira Barr MD
Sid Barsky MD
Gregory J. Basura MD, Ph.D
Donald Belsito MD
Jeffrey D. Bernhard MD
Jesse Berry MD
Victor Blanco MD
Benjamin R. Bohaty MD
William Bonnez MD
Mina Botros MD
Jeremy S. Boyd MD
Sarah Brenner MD
Robert A. Briggaman MD
Robert Brodell MD
Roman Bronfenbrener MD
Walter Brooks MD
Daniel Bryan MD
William Buckley MD
Philip Bulterys MD, PhD
Susan Burgin MD
Sonya Burton MD
Sean P. Bush MD, FACEP
Jeffrey Callen MD
Scott Camazine MD
Michael Cardwell
Shelley D. Cathcart MD
Robert Chalmers MD, MRCP, FRCP
Chia-Yu Chu MD, PhD
Flavio Ciferri MD
Maria Rosa Cordisco MD
Noah Craft MD, PhD
John T. Crissey MD
Harold E. Cross MD, PhD
Charles E. Crutchfield III MD
Adriana Cruz MD
Donna Culton MD, PhD
Bart J. Currie MBBS, FRACP, DTM&H
Chicky Dadlani MD
Alexander Dane DO
Roxana Daneshjou MD
C. Ralph Daniel III MD
Thomas Darling MD, PhD
William Delaney MD
Shreya Deoghare MD
Alex Derstenfeld
Damian P. DiCostanzo MD
Benedict F. DiGiovanni MD
Ncoza Dlova MD
Erin Doudt
James Earls MD
Libby Edwards MD
Melissa K. Egge MD
Charles N. Ellis MD
Rachel Ellis MD
David Elpern MD
Nancy Esterly MD
Stephen Estes MD
E. Dale Everett MD
Janet Fairley MD
David Feingold MD
Jennifer J. Findeis-Hosey MD
Benjamin Fisher MD
Robert Warne Fitch, MD
Henry Foong MBBS, FRCP
David Foster MD, MPH
Lindy P. Fox MD
Brian D. Foy PhD
Michael Franzblau MD
Vincent Fulginiti MD
Sunir J. Garg MD, FACS
Kevin J. Geary MD
Sharon Glick MD
Lowell Goldsmith MD, MPH
Sethuraman Gomathy MD
Bernardo Gontijo MD, PhD
Ayman Grada MD
Kenneth Greer MD
Kenneth G. Gross MD
Alan Gruber MD
Nathan D. Gundacker MD
Akshya Gupta MD
Vidal Haddad MSC, PhD, MD
Edward Halperin MD, MA
Ronald Hansen MD
John Harvey
Rizwan Hassan MD
Michael Hawke MD
Jason E. Hawkes MD
Peter W. Heald MD
Martha Hickman MD
David G. Hicks MD
Sarah Hocker DO
Ryan J. Hoefen MD, PhD
Li-Yang Hsu MD
Jennifer Huang MD
William W. Huang MD, MPH, FAAD
Eric F. Ingerowski MD
Sanjana Iyengar MD
Alvin H. Jacobs MD
Randy Jacobs MD, FAAD
Saagar Jadeja MD
Shahbaz A. Janjua MD
Joshua J. Jarvis MD
Noman Javed, MD
Beverly A. Johnson MD
Kit Johnson
Zachary John Jones MD
Harsimran Kaur MD
Robert Kalb MD
Katherine Kaproth-Joslin MD, PhD
Philip J. Katzman MD
A. Paul Kelly MD
Henry Kempe MD
Loren Ketai MD
Sidney Klaus MD
Ashwin Kosambia MD
Jessica A. Kozel MD
Carl Krucke
Mario E. Lacouture MD
Joseph Lam MD
Alfred T. Lane MD
Gerald S. Lazarus MD
Edith Lederman MD
Nahyoung Grace Lee MD
Ronald J. Lee MD
Pedro Legua MD, PhD
Robert Levin MD
Bethany Lewis MD
Sue Lewis-Jones FRCP, FRCPCH
Taisheng Li MD
Christine Liang MD
Shari Lipner MD, PhD
Adam Lipworth MD
Jenna Lullo MD
Jason Maguire MD
Mark Malek MD, MPH
Jere Mammino DO
Ricardo Mandojana MD
Lynne Margesson MD
Thomas J. Marrie MD
Maydel Martinez MD
Ralph Massey MD
Patrick McCleskey MD
Lynn McKinley-Grant MD
Karen McKoy MD
Thomas McMeekin MD
Josette McMichael MD
Somchai Meesiri MD
Joseph F. Merola MD
Mary Gail Mercurio MD
Anis Miladi MD
Larry E. Millikan MD
Dan Milner Jr. MD
Zaw Min MD
Nequesha Mohamed MD
Stephanie Montero
Alastair Moore MD
Keith Morley MD
Dean Morrell MD
Samuel Moschella MD
Surya N. Mundluru MD
Nicholas Erick Nacca MD
Rehan Naseemuddin MD
Taimor Nawaz MD
Vic Newcomer MD
John Nguyen MD
Matilda Nicholas MD, PhD
Thomas P. Nigra MD
Dylan Norton MD
Steven Oberlender MD, PhD
Maria Teresa Ochoa MD
Edward O'Keefe ND
Daniel C. Oppenheimer MD
Art Papier MD
Lawrence Parish MD
Tanner Parrent MD
Mukesh Patel MD
Lauren Patty-Daskivich MD
David Peng MD, MPH
Robert Penne MD
Nitipong Permpalung MD
Frank Johannes Plate MD, PhD
Miriam Pomeranz MD
Doug Powell MD
Harold S. Rabinovitz MD
Christopher J. Rapuano MD
Sireesha Reddy MD
Angela Restrepo MD, PhD
Cynthia Reyes-Barron MD
Bertrand Richert MD, PhD
J. Martin Rodriguez, MD, FACP
Theodore Rosen MD
Misha Rosenbach MD
Scott Schiffman MD
Robert H. Schosser MD
Glynis A. Scott MD
Carlos Seas MD, MSc
Deniz Seçkin MD
Daniel Sexton MD
Paul K. Shitabata MD
Tor Shwayder MD, FAAP, FAAD
Daniel Siegel, MD
Elaine Siegfried MD
Gene Sienkiewicz MD
Christye Sisson
Jonathan Soh MD
Philip I. Song MD
Mary J. Spencer MD, FAAP
Lawrence B. Stack MD
Sarah Stein MD
William Van Stoecker MD
Frances J. Storrs MD
Erik J. Stratman MD
Lindsay C. Strowd MD
Erika Summers MD
Belinda Tan MD, PhD
Robert Tomsick MD
Hensin Tsao MD, PhD
Richard P. Usatine MD
Jenny Valverde MD
Vishalakshi Viswanath MD
Susan Voci MD
Lisa Wallin ANP, FCCWS
Douglas Walsh MD
Ryan R. Walsh MD
George Watt MD
Erin X. Wei MD
Clayton E. Wheeler MD
Sally-Ann Whelan MS, NP, CWOCN
Danielle Wilbur MD
Jan Willems MD, PhD
Victoria L. Williams MD
James Henry Willig MD, MPH
Kelly Wilmas MD
Karen Wiss MD
Vivian Wong MD, PhD
Sook-Bin Woo MS, DMD, MMSc
Jamie Woodcock MD
Stephen J. Xenias MD
Nathaniel Yohannes
Lisa Zaba MD
Vijay Zawar MD
Bonnnie Zhang MD
Carolyn Ziemer MD
Barret Zimmerman MD
Jeffrey P. Zwerner MD, PhD
Organizations
American Academy of Dermatology
Am. Journal of Trop. Med & Hygiene
Armed Forces Pest Management Board
Blackwell Publishing
Broward Health Medical Center
Bugwood Network
Centers For Disease Control and Prevention
Centro Internacional de Entrenamiento e Investigaciones Mèdicas (CIDEIM)
Dermatology Associates of Concord
Dermatology Online Journal
East Carolina University (ECU), Division of Dermatology
International Atomic Energy Agency
Massachusetts Medical Society
NYU Department of Dermatology
Oregon Health & Science University (OHSU)
Oxford University Press
Radiological Society of North America
Washington Hospital Center
Wikipedia
World Health Organization
Common Features
Addison disease is a chronic primary adrenocortical insufficiency resulting from dysfunction of the adrenal glands. This can be due to a variety of causes, which include autoimmune diseases, infections (tuberculosis), and neoplasms (metastatic cancer). The most common associated autoimmune diseases are Type I diabetes mellitus, Hashimoto thyroiditis, and vitiligo. Patients with acquired immunodeficiency syndrome may develop Addison disease due to cytomegalovirus infection. Other less common causes are drugs (antifungals), congenital adrenal hypoplasia, and disorders such as sarcoidosis and amyloidosis. Some cases are idiopathic. Patients with loss-of-function mutations in sphingosine-1-phosphate lyase may have nephrosis with ichthyosis and adrenal insufficiency.
The adrenal insufficiency leads to decreased levels of glucocorticoids (the most common), mineralocorticoids, and adrenal androgens. The disease is characterized by general symptoms of fatigue, weight loss, weakness, vomiting, dizziness, cold intolerance, and muscle aches. Because these symptoms are nonspecific, the diagnosis may go unrecognized until the patient presents with a life-threatening adrenal crisis (severe hypotension and even coma).
The cutaneous manifestation of patients with chronic Addison disease is hyperpigmentation of skin and mucous membranes. Skin pigmentation, which appears as "bronzing" of the skin, is generalized and mainly affects sun-exposed areas. Oral mucosal lesions present as dark brown to black macules and frequently are the first sign of disease. These and the other clinical signs of the disease appear only after 90% of the adrenal gland is nonfunctioning. The hyperpigmentation is due to increased production of melanocyte-stimulating hormone (MSH), which is part of the adrenocorticotrophic hormone (ACTH) molecule; ACTH production in the pituitary increases in response to decreased cortisol production, leading also to an increase in MSH levels and melanosis.
Men and women are equally affected, and although all ages are affected, it is more common between the ages of 30 and 50. Estimated prevalence of the disease is at 120 per million.
Addisonian Crisis: Acute adrenal failure presents with severe penetrating abdominal pain accompanied by vomiting and diarrhea, low blood pressure, and loss of consciousness. This is a life-threatening emergency that must be managed aggressively.
Diseases that produce pigmentation of the oral mucosa have to be differentiated from Addison disease.
Physiologic pigmentation (see multifocal or diffuse mucosal pigmentation) – Although this appears similar to pigmentation of Addison disease, this is not of acute onset and is unaccompanied by systemic symptoms.
McCune-Albright syndrome and neurofibromatosis are both associated with oral melanotic macules and café au lait skin pigmentation.
Post-inflammatory hypermelanosis and smoker's melanosis occur as a result of inflammation and appear gradually over time; it is particularly common in areas of lichen planus that develop in dark-skinned patients.
Melanoacanthosis may be a form of post-inflammatory hypermelanosis that has a sudden onset, spreads rapidly, and then resolves.
Oral melanotic macules are common on the vermilion, palatal mucosa, and gingiva and are solitary or multi-focal, appearing gradually over time.
Medications such as minocycline, anti-malarials, clofazimine, and imatinib may cause pigmentation, often on the palatal mucosa. Tetracycline pigmentation of teeth show through the mucosa as a grayish macular discoloration.
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Drug Reaction Data
Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.