Minocycline-induced Hyperpigmentation Research Articles

Minocycline-Induced Hyperpigmentation in a Patient with Multiple Causes of Skin Discoloration

Minocycline-Induced Hyperpigmentation in a Patient with Multiple Causes of Skin Discoloration

Minocycline-induced Hyperpigmentation Confined to Lupus Miliaris Disseminatus Faciei.

Abstract is missing (Short communication)

A rare case of minocycline induced diffuse hyperpigmentation

Minocycline, a tetracycline group of antibiotics, is commonly used to treat various infections, dermatological conditions and rarely used to treat rheumatoid arthritis. Prolonged use of minocycline in higher doses can rarely cause skin hyperpigmentation. Minocycline-induced hyperpigmentation can also involve the sclera and retina in the eyes.

Minocycline-Induced Hyperpigmentation: Importance of Early Diagnosis

A 75-year-old woman on hemodialysis for end-stage renal failure due to polycystic kidney disease developed dark spots on her limbs. She had been treated for extended spectrum beta-lactamase–producing Escherichia coli bacteremia by a rectovaginal fistula and was on long-term oral minocycline (cumulative dose 45 g). Physical examination revealed dark patches on her forearms and lower legs but no trunk hyperpigmentation or visual impairment. Blood tests were normal. Skin biopsy confirmed minocycline-induced hyperpigmentation. Minocycline-induced pigmentation is categorized into types I–IV, each with unique clinical and histopathological features. Types I and II are reversible upon discontinuing minocycline, whereas types III and IV are permanent. The patient was diagnosed with type II pigmentation, generally occurring with a cumulative dose exceeding 70–100 g; however, her lower dose (45 g) led to pigmentation, possibly influenced by her vitamin D deficiency. Clinicians should evaluate the antimicrobial indication and treatment period, considering not only the benefits but also the side effects and antimicrobial resistance. If minocycline is used, attention should be paid to minocycline-induced hyperpigmentation, and this possibility should be communicated to patients to enable early detection.

Minocycline-induced Conjunctival Hyperpigmentation.

A 73-year-old woman presented with a 1-year history of pigmented conjunctival lesions in both eyes. She had been taking minocycline for decades for recurrent facial cysts. On examination, she had a larger pigmented cystic lesion of her right inferior fornix conjunctiva, and several smaller hyperpigmented lesions in her right inferior, left superior, and left inferior palpebral conjunctivae (Panel A; external photograph). She underwent an excisional biopsy of the large cyst. Pathology showed exogenous brownish-gray pigment granules (circle) deposited in macrophages surrounding vessels in the substantia propia (Panel B; hematoxylin & eosin-stained image at 40× magnification). The pigment granules were stained black (arrow) with Fontana-Masson stain (Panel C; image at 40×). There was no evidence of an atypical melanocytic proliferation. A diagnosis of minocycline-induced hyperpigmentation was made. Minocycline, a tetracycline antibiotic, can be used to treat dermatologic conditions. Extended use can lead to hyperpigmentation of the skin, nails, teeth, oral mucosa, sclera, and conjunctiva. There is a wide range of reported doses and duration of therapy associated with mucosal or cutaneous hyperpigmentation varying by type and site, occurring as early as days to weeks, with a median onset of 1–2 years. Cosmetic concerns should prompt discontinuation, although hyperpigmentation is likely permanent. These lesions were not visually significant nor bothersome, and therefore no additional treatment was recommended.

Type II minocycline-induced cutaneous and scleral hyperpigmentation.

Type II minocycline-induced cutaneous and scleral hyperpigmentation.

Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation-The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation.

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

Blue nails: a case of minocycline-induced hyperpigmentation

Blue nails: a case of minocycline-induced hyperpigmentation

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

Minocycline is a tetracycline group antibiotic that is known to cause significant antibacterial and anti-inflammatory effects. Minocycline has been widely used to treat systemic infection, acne, dermatitis, and rosacea. However, various dose-related side effects of hyperpigmentation in whole body tissues have been reported. Three main types of minocycline-induced hyperpigmentation have been identified. In rare severe hyperpigmentation cases, drug-induced hyperpigmentation can mimic local cellulitis or peripheral arterial occlusive disease (PAOD). These processes require different therapeutic strategies. Therefore, early diagnosis is extremely important for physicians to determine the etiology of the hyperpigmentation, and subsequently discontinue the minocycline if indicated. We describe a rare case presenting a severe form of type III minocycline-induced hyperpigmentation mimicking peripheral arterial occlusive disease in a bullous pemphigoid patient.

Minocycline-induced hyperpigmentation.

Minocycline-induced hyperpigmentation.

Swept-Source Optical Coherence Tomography and OCT Angiography of Minocycline-Induced Retinal and Systemic Hyperpigmentation

This is a report of an 80-year-old man with a history of rosacea and rhinophyma treated for 15 years with oral minocycline who developed significant minocycline-induced hyperpigmentation. He also had a history of Fuchs' endothelial dystrophy and had undergone penetrating keratoplasty in the right eye. Best-corrected visual acuity was 20/60 in both eyes. Examination revealed slate-grey hyperpigmentation of his body, face, and sclera and black, confluent pigmentation in the central maculae of both eyes. Green wavelength fundus autofluorescence demonstrated speckled hyperautofluorescence in the right eye, and swept-source OCT and OCTA demonstrated pigmented epithelial detachments and significant signal blocking without choroidal neovascularization.

Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects

Minocycline is a tetracycline derivative antibiotic commonly prescribed for acne, rosacea, and other inflammatory skin disorders. Minocycline turns black when oxidized, leading to discoloration of the skin, nails, bulbar conjunctiva, oral mucosa, teeth, bones, and thyroid gland. Hyperpigmentation has been reported after long-term minocycline therapy with at least 100 mg/day. Three types of minocycline-induced cutaneous hyperpigmentation can result. Type I is the most common, and is associated with blue-black discoloration in areas of previous inflammation and scarring. Type II most commonly affects the legs and is characterized by blue-gray pigmentation of previously normal skin. Type III is the least common and is characterized by diffuse muddy-brown discoloration predominantly on sun exposed skin. Minocycline-induced hyperpigmentation may be cosmetically disfiguring and prompt identification is essential. Without treatment, symptoms may take several months, to years to resolve, after discontinuation of the drug. However, the pigmentation may never completely disappear. In fact, there have been few reports of complete resolution associated with any therapeutic intervention. We report a case of a patient on long-term minocycline therapy utilized as an anti-inflammatory agent to control symptoms of rheumatoid arthritis, which led to minocycline-induced hyperpigmentation of the face. To remove the blue-gray cutaneous deposits, 3 Q-switched lasers (Neodymium: yttrium aluminum garnet (Nd:YAG) 1064 nm, Alexandrite 755 nm, and Ruby 694 nm) were used in test areas. The Alexandrite 755 nm laser proved to provide effective clearing of the minocycline hyperpigmentation requiring just 2 treatments, with minimal treatment discomfort and down time.

Minocycline-Induced Hyperpigmentation in Multibacillary Leprosy

Minocycline has been used in the treatment of leprosy since the demonstration of its efficacy in inhibiting Mycobacterium leprae growth in 1987. Hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical and histological patterns: type I consists of blue-black pigmentation in areas of current or previous inflammation, type II consists of blue-gray pigmentation of normal skin, often seen on the legs, and type III consists of diffuse muddy-brown pigmentation accentuated on sun-exposed sites. Whereas type I hyperpigmentation stains positively for hemosiderin and type III hyperpigmentation stains positively for melanin, type II hyperpigmentation stains positively for both. We describe 2 patients with leprosy on minocycline therapy who developed multiple patches of blue-gray pigmentation within preexisting leprosy lesions. Biopsies from both patients demonstrated deposition of brownish-black pigment granules within the cytoplasm of foamy histiocytes that was highlighted by both Perls and Fontana-Masson stains. Given the clinical and histological findings in our patients, it is as yet unclear whether this coexistent type I clinical pattern and type II histopathologic pattern of pigmentation is unique to multibacillary leprosy. These findings provide support for the existence of additional subtypes of minocycline-induced hyperpigmentation that do not adhere to the classic 3-type model described.

Minocycline-induced Hyperpigmentation : Under-recognized Side Effect of Minocycline Therapy

Minocycline-induced Hyperpigmentation : Under-recognized Side Effect of Minocycline Therapy

Minocycline-Induced Hyperpigmentation in Rheumatoid Arthritis

Minocycline is recognized as an effective, well-tolerated therapy in rheumatoid arthritis (RA), although its use has been associated with the development of cutaneous hyperpigmentation. To assess the clinical determinants and frequency of minocycline-induced hyperpigmentation in patients with RA. A retrospective medical record review of all patients with RA seen in 2 academic rheumatology practices was performed to identify subjects who had received at least 1 month of continuous minocycline therapy. Patient demographics, disease characteristics, medication use, and medication side effects were abstracted from the medical record. Using Cox proportional hazards regression and restricting the analysis to the initial minocycline course, we examined the association of patient factors and concomitant medications with the development of hyperpigmentation. Of 121 patients with at least 1 minocycline course of 30 days or more, 44 (36%) developed documented hyperpigmentation, including 33 during the initial course over a median duration of 9.1 month (range 2.2-77.8 months). Hyperpigmentation was most commonly seen on the upper and lower extremities and the head/neck region. Minocycline-induced hyperpigmentation led to the discontinuation of treatment in 3 patients, with 12 additional patients receiving a dose reduction. Increasing age was the only clinical determinant significantly associated with hyperpigmentation (HR = 1.04; 95% CI 1.00-1.07, P = 0.04). There were no significant associations of sex, weight, concomitant prednisone, or aspirin use with the development of hyperpigmentation. Minocycline-induced hyperpigmentation is a common complication seen with minocycline use in the treatment of RA, and seems to increase with age.

Minocycline-Induced Hyperpigmentation

This 89-year-old woman presented with a nonhealing leg ulcer. She was taking minocycline twice a day as suppressive therapy after orthopedic fixation of a hip fracture 28 months earlier.

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

Alkaptonuria, a rare autosomal-recessive disorder caused by mutations in the HGD gene and a deficiency of homogentisate 1,2-dioxygenase, is characterized by accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue resulting in joint disease. Certain medications have been reported to cause cutaneous hyperpigmentation resembling that of alkaptonuria. We present 5 such cases. Eighty-eight patients with a possible diagnosis of alkaptonuria were examined at the National Institutes of Health Clinical Center between June 2000 and March 2004. The diagnosis of alkaptonuria was confirmed or ruled out by measurement of HGA in the urine. Five patients with findings consistent with ochronosis, including pigmentary changes of the ear and mild degenerative disease of the spine and large joints, were diagnosed clinically as having alkaptonuria, but the diagnosis was withdrawn based on normal urine HGA levels. All 5 patients were women who had taken minocycline for dermatologic or rheumatologic disorders for extended periods. Minocycline-induced hyperpigmentation should be considered in the differential diagnosis of ochronosis. This could be of increased significance now that minocycline and other tetracyclines have been proposed as therapeutic options for rheumatoid arthritis, bringing a new population of patients with ochronosis and arthritis to medical attention with the potential, but incorrect, diagnosis of alkaptonuria.

Minocycline-induced hyperpigmentation treated with a 755-nm Q-switched alexandrite laser.

Cutaneous pigmentation associated with minocycline therapy is an unusual adverse effect for which few successful treatments have been described. The pigment changes may persist for years, despite cessation of therapy, and is often cosmetically disfiguring, causing significant embarrassment and psychological depression in those affected. Few safe and effective treatments have been described in the past; however, recent pigment-specific laser technology has shown promise in the treatment of this condition. The objective was to describe a series of patients with minocycline-induced hyperpigmentation who were successfully treated with a 755-nm Q-switched alexandrite laser. Six patients with minocycline-induced hyperpigmentation on the face or legs were treated with a Q-switched alexandrite laser on a bimonthly basis until pigmentation was eradicated. Cutaneous pigmentation resolved completely in all patients in an average of four laser sessions. Side effects were limited to transient purpura and mild desquamation without scarring or dyspigmentation. Minocycline-induced cutaneous pigmentation can be effectively cleared without risk of adverse sequelae by Q-switched alexandrite (755-nm) laser irradiation.

Minocycline-Induced Hyperpigmentation Treated with a 755-nm Q-Switched Alexandrite Laser

BACKGROUND Cutaneous pigmentation associated with minocycline therapy is an unusual adverse effect for which few successful treatments have been described. The pigment changes may persist for years, despite cessation of therapy, and is often cosmetically disfiguring, causing significant embarrassment and psychological depression in those affected. Few safe and effective treatments have been described in the past; however, recent pigment-specific laser technology has shown promise in the treatment of this condition. OBJECTIVE The objective was to describe a series of patients with minocycline-induced hyperpigmentation who were successfully treated with a 755-nm Q-switched alexandrite laser. METHODS Six patients with minocycline-induced hyperpigmentation on the face or legs were treated with a Q-switched alexandrite laser on a bimonthly basis until pigmentation was eradicated. RESULTS Cutaneous pigmentation resolved completely in all patients in an average of four laser sessions. Side effects were limited to transient purpura and mild desquamation without scarring or dyspigmentation. CONCLUSION Minocycline-induced cutaneous pigmentation can be effectively cleared without risk of adverse sequelae by Q-switched alexandrite (755-nm) laser irradiation.

Minocycline-induced hyperpigmentation resolves during oral isotretinoin therapy

Minocycline-induced hyperpigmentation resolves during oral isotretinoin therapy