ORIGINAL ARTICLE Minocycline-Induced Hyperpigmentation Treated with a 755-nm Q-Switched Alexandrite Laser TINA S. ALSTER,MD,AND SAMIR N. GUPTA,MD Washington, DC; and Toronto, Ontario, Canada BACKGROUND. Cutaneous pigmentation associated with minocyc- METHODS. Six patients with minocycline-induced hyperpigmen- line therapy is an unusual adverse effect for which few successful tation on the face or legs were treated with a Q-switched alex- treatments have been described. The pigment changes may persist andrite laser on a bimonthly basis until pigmentation was for years, despite cessation of therapy, and is often cosmetically eradicated. disfiguring, causing significant embarrassment and psychological RESULTS. Cutaneous pigmentation resolved completely in all depression in those affected. Few safe and effective treatments have patients in an average of four laser sessions. Side effects were been described in the past; however, recent pigment-specific laser limited to transient purpura and mild desquamation without technology has shown promise in the treatment of this condition. scarring or dyspigmentation. OBJECTIVE. The objective was to describe a series of patients CONCLUSION. Minocycline-induced cutaneous pigmentation with minocycline-induced hyperpigmentation who were suc- can be effectively cleared without risk of adverse sequelae by cessfully treated with a 755-nm Q-switched alexandrite laser. Q-switched alexandrite (755-nm) laser irradiation. TINA S. ALSTER, MD, AND SAMIR N. GUPTA, MD HAVE INDICATED NO SIGNIFICANT INTEREST WITH COMMER- CIAL SUPPORTERS. MINOCYCLINE IS a second-generation semisynthetic tation has been observed irrespective of dosage or tetracycline derivative that was first introduced in treatment duration.5 Noncutaneous sites where pig- 1967. It is a broad-spectrum antibiotic that inhibits mentation has also been reported include the oral mu- protein synthesis, causing bacteriostasis. It also reduc- cosa, nails, nail beds, teeth, conjunctiva, bones, sclera, es fatty acids in sebum and exhibits anti-inflammatory substantia nigra, atherosclerotic plaques, and heart effects, making it a popular treatment for acne-related valves.6–12 disorders.1 Its structure contains the same basic ring as Over the past several years, successful treatment of tetracycline, but it is chemically different with substi- cutaneous pigmentation with various pigment-specific tution of a dimethylamino group at C7 and absence of lasers has been reported. Q-switched ruby (694-nm), a functional group at C6, rendering it more lipophilic. alexandrite (755-nm), and Nd:YAG (532-/1064-nm) As a result, the drug’s distribution and half-life are lasers have been used with good clinical results and increased, enabling it to cross bacterial lipid mem- histologic clearing.13–21 We report our success treating branes readily. six consecutive patients with minocycline-induced pig- For the majority of patients, treatment with min- mentation using a Q-switched alexandrite (755-nm) ocycline is without consequence. Cutaneous adverse ef- laser. fects attributed to minocycline therapy include pruritus, photosensitivity, urticaria, and pigmentation, the latter being the most common (3%–14% incidence).2–4 Materials and Methods Minocycline is the only tetracycline derivative re- Six consecutive patients presenting with minocycline- ported to cause cutaneous pigmentation and has been induced hyperpigmentation were included for study. shown to occur 3 months to 5 years after initiation of 5 All patients demonstrated slate-gray pigmentation of treatment. Although most reported cases of cutaneous several cutaneous sites, including the face and legs. hyperpigmentation occur following a cumulative dose The onset of pigmentation was reported by patients of 50 g or more of drug, minocycline-induced pigmen- within 6 months to 8 years of their oral minocycline course (Table 1). Address correspondence and reprint requests to: Tina S. Alster, MD, Patients were each treated by a single operator Director, Washington Institute of Dermatologic Laser Surgery, 2311 M (T.A.) with a Q-switched 755-nm alexandrite laser Street, NW, Suite 200, Washington, DC 20037, or e-mail: (AlexLAZR, Candela Laser Corp., Wayland, MA) at 2 [email protected]. energy densities ranging from 6.5 to 8.5 J/cm (mean r 2004 by the American Society for Dermatologic Surgery, Inc. Published by Blackwell Publishing, Inc. ISSN: 1076-0512/04/$15.00/0 Dermatol Surg 2004;30:1201–1204 1202 ALSTER AND GUPTA: Q-SWITCHED ALEXANDRITE LASER HYPERPIGMENTATION TREATMENT Dermatol Surg 30:9:September 2004 Table1. Patient Characteristics Patient Sex Age (Years) Skin Phototype Pigment Location Duration of Minocycline Treatment 1 F 52 II Cheeks, chin, lip, ears 8 years 2 F 51 II Cheeks 6 months 3 F 53 II Upper lip 1 years 4 M 44 II Cheeks 2 years 5 F 48 III Legs 10 months 6 F 47 II Cheeks 1 years 7.5 J/cm2) using a 3-mm collimated spot and 50-ms (Table 2; Figures 1 and 2). Continual skin lightening pulse duration. Adjacent, nonoverlapping laser pulses was noted after each laser session for several weeks, were delivered over the involved skin regions, produc- but stabilized within the 2-month interval between ing an ash-white tissue response without bleeding. treatments. Side effects of laser treatment were limited Topical antibiotic ointment (Bacitracin zinc, E. Fou- to localized purpura and mild desquamation for 3 to 5 gera & Co, Melville, NY) was applied immediately days after irradiation. No vesiculation, dyspigmenta- after treatment and repeated daily until healing was tion, or scarring were seen in any patient. completed (5–7 days). Treatments were delivered on a bimonthly basis until pigmentation was totally re- solved. Patients were evaluated at each visit for evi- dence of dyspigmentation, scarring, or other untoward effects from the laser treatment. Results Cutaneous pigmentation resolved completely in all patients within three to five (mean four) laser sessions Table2. Laser Treatment Sessions and Parameters Patient Number of Treatments Fluences, J/cm2 (Mean) 1 4 6.5 (6.5) 2 3 6.5–7.5 (7.0) 3 4 6.5–8.0 (7.25) 4 4 6.5–8.0 (7.25) 5 4 6.5–8.0 (7.25) Figure 2. Blue-gray pigmentation on the ear in Patient 1 before treat- ment (left) and after four 755-nm Q-switched alexandrite laser sessions 6 5 6.5–8.5 (7.5) (right). Figure 1. (A) Minocycline pigmentation on the cheeks, upper lip, and chin (Patient 1) before treatment. (B) After four Q-switched alexandrite laser treatments, complete removal of pigmentation was achieved. Dermatol Surg 30:9:September 2004 ALSTER AND GUPTA: Q-SWITCHED ALEXANDRITE LASER HYPERPIGMENTATION TREATMENT 1203 Discussion for pigment clearing and dermal recovery. Although the use of any Q-switched pigment-specific laser sys- The pathophysiology of minocycline-induced pigment tem, including the ruby, alexandrite, and Nd:YAG is unknown. On histologic examination of tissue the systems, would be expected to adequately remove cutaneous pigment has been identified as iron, mela- minocycline-induced dermal pigment, the alexandrite nin, or minocycline particles.22–24 It is possible that laser tends to produce less tissue splatter than the pigment formation could occur through polymeriza- Nd:YAG laser intraoperatively and be less prone to tion in a process analogous to melanogenesis from postoperative hypopigmentation than the ruby sys- dopa, given that crystalline minocycline turns black tem.15,16 There have also been reports of other drug- when oxidized. induced pigmentations (e.g., from imipramine and Clinically, minocycline-induced hyperpigmentation amiodarone) similarly responsive to Q-switched laser presents as a bluish discoloration of the skin. Three irradiation.31,32 Upon literature review, it was also patterns of hyperpigmentation, each with differing interesting to note a report of chrysiasis induced by composition and location of the pigment particles in Q-switched laser treatment in a patient with a remote the skin, have been described.22 Patients may present history of oral gold ingestion for arthritis.33 The re- with a combination of the different patterns. The first moval of pigmentation in this latter case was achieved pattern (type I) displays dose-dependent, blue-black after reflectance spectrophotometry and clinical testing pigmentation in sites of inflammation, scarring, or demonstrated that only a long-pulsed system with previously traumatized skin. In this pattern, histologic wavelengths ranging from 550 to 850 nm could be used. evaluation shows intracellular and extracellular der- mal pigment staining positively for iron. The second pattern (type II) is characterized by non-dose-depend- Conclusions ent, blue-gray pigmentation in clinically normal skin, usually of the anterior tibiae and forearms. Histolog- Minocycline-induced cutaneous pigmentation can be ically, intracellular pigment is seen in the dermis and effectively cleared without risk of adverse sequelae by the subcutis stains positively for melanin and iron. The Q-switched alexandrite (755-nm) laser irradiation. Fur- third pattern (type III) presents as a generalized mud- ther investigation into the specific skin reflectance and dy-brown pigmentation in photosensitive areas, with optimal absorption spectrum of minocycline pigmenta- positive staining for melanin in the epidermis and tion may help to further our understanding of the var- upper dermis. Although all but one of the patients ious types of pigmentation involved with this condition described herein falls in the third pattern (with pig- and better optimize laser