A 77-year-old male was referred for venous insufficiency after presenting with skin hyperpigmentation and mild lower extremity edema after a two-week golf vacation. His medical comorbidities included non-melanoma skin cancer, atrial fibrillation, hypertension, coronary artery disease, and degenerative arthritis. The patient also had been prescribed 100 mg of minocycline orally twice a day for the past three months as suppressive therapy after developing a polymicrobial left total knee arthroplasty infection. His physical examination revealed non-palpable, non-pruritic blue-gray patches of hyperpigmentation on his lower extremities and forearms bilaterally (Figures 1, 2, 3, 4). Complete blood count, chemistries, and liver function studies were normal. Venous ultrasound performed prior to his visit demonstrated patency of the right great saphenous vein and small saphenous vein without significant reflux, but severe incompetence of the left great saphenous vein from the upper thigh to the calf.
Figure 1
Figure 2
Figure 3
Figure 4
Which of the following is the best next step in the management of this patient's cutaneous hyperpigmentation?
Show Answer
The correct answer is: B. Change antimicrobial therapy due to drug-induced hyperpigmentation.
Based on the clinical history of minocycline use, minocycline-induced hyperpigmentation was diagnosed, and the antimicrobial therapy was changed to doxycycline. There are several medications that can cause hyperpigmentation, including bleomycin, amiodarone, zidovudine, imipramine, hydroxychloroquine, verapamil, and minocycline. Minocycline-induced cutaneous hyperpigmentation is a well-documented adverse effect of this antibiotic that is frequently used for the treatment of acne, rosacea, rheumatoid arthritis, and orthopedic infections; the cumulative incidence ranging between 2-28%, 36-41%, and 54%, respectively.1-3 Mechanisms of cutaneous hyperpigmentation from minocycline include oxidation of metabolites, enhancement of melanocytes, and deposition of insoluble minocycline-iron complex's.4 Minocycline can also affect the alveolar ridges of the mouth, palate, sclera of the eye, thyroid gland, teeth, bones, and heart valves through pigment deposition.4-7 Cutaneous hyperpigmentation from minocycline is typically associated with a higher cumulative dosage of greater than 100 grams or increased duration of use. Minocycline hyperpigmentation is classified into four types: type I-blue-black discoloration within acne scars; type II-blue-gray pigmentation on the extremities; type III- muddy brown discoloration on sun-exposed areas; and type IV-hyperpigmentation within unexposed scar tissue.8 This patient clinically exhibited type II minocycline-induced hyperpigmentation. Early recognition is important, since cutaneous hyperpigmentation may take months to years to fade after minocycline use is discontinued.9
References
Dereure O. Drug-induced skin pigmentation. Am J Clin Dermatol 2001;2:253-62.
Taveres J, Leung W. Discoloration of nail beds and skin from minocycline. CMAJ 2011;183:224.
Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. Open Forum Infect Dis 2016;3.
Zuckerman M, Boyle K, Rosenbaum C. Minocycline toxicity: case files of the University of Massachusetts medical toxicology fellowship. J Med Toxicol 2012;8:304-9.
Tsunekawa T, Jones K, Doty J. Black pigmented aortic valve and sinus of Valsalva caused by life-long minocycline therapy. Interact Cardiovasc Thorac Surg 2014;19:339-40.
Joshi H, Chhikara V, Arya K, Pathak R. Some undesirable effects reported in past five years related to minocycline therapy: a review. Ann Biol Res 2010;1:64-71.
Filitis D, Graber E. Minocycline-induced hyperpigmentation involving the oral mucosa after short-term minocycline use. Cutis 2013;92:46-8.
Krause W. Drug-induced hyperpigmentation: a systematic review. J Dtsch Dermatol Ges 2013;11:644-51.
James WD, Elston DM, Berger TG. Andrews' Diseases of the Skin: Clinical Dermatology. 11th ed. Saunders/Elsevier; London, UK: 2011. p.126.
Log in to MyACC
