Minocycline‐induced cutaneous pigmentation

Abstract

A 76‐year‐old man receiving long‐term prednisone therapy for rheumatoid arthritis had a four‐part intertrochanteric fracture after a fall. The patient underwent an open reduction with internal fixation and dynamic hip screw placement. Two months later, when the patient presented with significant pain and difficulty ambulating, radiographs revealed dissociation of the compression screw from the femoral head. At the time of removal of failed hardware, a total hip replacement procedure was aborted when intraoperative findings were consistent with infection. Thorough irrigation and debridement were performed, with placement of antibiotic‐impregnated cement spacers. One month after a 4‐week course of intravenous cefazolin, the patient underwent left total hip arthroplasty. Intraoperative cultures grew methicillin‐resistant Staphylococcus aureus and Corynebacterium jeikeium. A 4‐week course of intravenous vancomycin was followed by long‐term antibiotic suppression with long‐term minocycline (100 mg twice daily). Six months after starting minocycline, the patient noticed a blue‐gray discoloration of the forearms. During the next 4 months, the pigmentation progressed considerably. He was admitted to Mayo Clinic for a myocardial infarction. Three‐vessel coronary artery disease was discovered, necessitating bypass grafting. Before surgery, dermatology was consulted. A main concern of the primary service was the discoloration representing ecchymoses in a surgical candidate with a possible bleeding diathesis. Cutaneous examination revealed slate gray, ill‐defined patches in the preauricular, flank, upper thigh, and shoulder areas. Similar patches coalesced on the upper and lower extremities (Fig. 1). There was no scleral or mucous membrane involvement. Histologically, minocycline pigmentation with pigment‐laden macrophages and free dermal pigment in the papillary and superficial reticular dermis stained positive with Prussian blue and Fontana‐Masson (Fig. 2). Minocycline was discontinued, and the patient was started on trimethoprim‐sulfamethoxazole double strength once daily for long‐term antimicrobial therapy. 1 Minocycline‐induced slate gray discoloration of the (a) arms and (b) shins 2 Pigment‐laden macrophages and free dermal pigment. (Hematoxylin‐eosin; original magnification ×600)

Minocycline protects melanocytes against H2O2-inducedcell death via JNK and p38 MAPK pathways

“…We propose that minocycline has no direct effects on melanin synthesis or tyrosinase activity (data not shown), and the up-regulated melanin synthesis by minocycline is most likely a consequence of an increase of melanocyte viability. Collective data from clinical application have revealed that skin pigmentation occurs in some rheumatoid patients with chronic minocycline administration (36,37). Although the underlying mechanism has not yet been elucidated, it has been observed that minocyclineinduced pigment deposit in papillary dermis but not in epidermis has been observed (38,39).…”

Severe Type of Minocycline-Induced Hyperpigmentation Mimicking Peripheral Arterial Occlusive Disease in a Bullous Pemphigoid Patient

“…Type III pigmentation presents with diffuse muddy-brown discoloration on photo-exposed skin [23]. In types II and III pigmentation, there is an association between the duration of minocycline intake and the duration of pigmentation reported, with the median duration lasting more than 9 months with cumulative doses [10,24,25,26].…”

Minocycline‐induced hyperpigmentation masquerading as alkaptonuria in individuals with joint pain

“…Type III appears muddy‐brown, developing in a generalized, symmetric pattern and accentuated in areas of sun exposure (6). In both alkaptonuria and minocycline‐induced hyperpigmentation, the pigment deposited is believed to resemble melanin (4, 9). If a patient is found to have hyperpigmentation secondary to minocycline, the medication should be stopped to prevent further pigment accumulation.…”