Woman’s Tongue Turns Brown After Course of Antibiotics

A 69-year-old woman presented to a medical clinic due to a brown “stain” on her tongue that had developed about 10 days previously. She was not feverish, and had not experienced any nausea or changes in taste. She was not a smoker or a drinker. She had no changes in medication, and she denied use of herbal/traditional Chinese medicine, oxidizing/irritant mouthwashes, tongue cleaners, or tongue scrapers.

Her medical history included high blood pressure, hyperlipidemia, diabetes mellitus, and osteoporosis. She had also been diagnosed with mixed connective tissue disease, for which she was taking oral prednisolone 5 mg once daily.

The patient’s more recent medical history included MRI-diagnosed tenosynovitis of the right index and middle finger flexor, complicated by osteomyelitis due to Mycobacterium chelonae. About 3 months before she presented to the clinic, this had been managed with debridement and reconstructive surgery. Because of the bacterial infection, she had also been started on a regimen of intravenous tobramycin and imipenem and oral clarithromycin. She took these antibiotics for 6 weeks before switching to oral moxifloxacin and clarithromycin. Ten days later, she noticed the brown discoloration of her tongue and presented to the clinic.

A physical examination found that the patient was in good general health: her blood pressure was 135/76 mm Hg, pulse 80 beats per minute, respiration rate 15 breaths per minute, and body temperature 36.7°C. The oral mucosa was dry and there was very little pooled saliva on the floor of her mouth. Clinicians noted brown discoloration on the dorsum of the tongue, with carpet-like elongated filiform lingual papillae (Figure 1).

She had no evidence of tooth decay, halitosis, discharge, bleeding, or exudates, and the gingiva was healthy and intact. She did not use dentures. Clinicians found that her right finger had healed and all other clinical examinations were unremarkable.

Laboratory test results revealed mild anemia (hemoglobin, 11.5 g/dL), a white blood cell count of 9,800/mm³, erythrocyte sedimentation rate of 20 mm per hour, and C-reactive protein level of 1.0 mg/dL.

There were no symptoms to warrant a tongue swab culture. The discoloration had developed over about a 10-day period, which helped rule out possible diagnoses such as oral hairy leukoplakia or acanthosis nigricans. Clinicians arrived at a tentative diagnosis of stained tongue due to foods, or black hairy tongue (BHT) from antibiotics. They instructed the patient regarding daily oral hygiene and tongue scraping and she was observed for the following 2 weeks.

However, the discoloration and elongated filiform lingual papillae of her tongue persisted. In planning next steps, clinicians advised her regarding the lower susceptibility of moxifloxacin than clarithromycin for isolated Mycobacterium chelonae. She opted to stop taking moxifloxacin and continued clarithromycin as monotherapy. Her tongue returned to normal within 2 days of discontinuing moxifloxacin (Figure 2). Follow-up 12 months later showed no evidence of tenosynovitis recurrence.

Discussion

Clinicians reporting this case urged their colleagues to be aware of “agents or lifestyles that may cause BHT,” and noted the importance of advising patients of the possibility of this acquired benign reaction before using treatments that might cause this condition, to avoid patient anxiety or premature treatment cessation.

Classically BHT (also called lingua villosa nigra) presents as “a superficial black and hairy carpet-like lingual growth” first described in the 16th century as “hairs on the tongue that would regrow upon being removed,” the case authors noted.

BHT is relatively uncommon, with a reported prevalence ranging from 0.6% to 11.3%, the authors wrote, depending on age, sex, ethnicity, and study population, as well as on intrinsic or extrinsic contributors.

Although factors involved in development of BHT are not fully understood, it appears to occur because “defective desquamation of the dorsal tongue surface … prevents normal debridement, leading to the accumulation of keratinized layers,” the group explained.

This leads to hypertrophy and elongation of superficial hair-like filiform papillae which then can accumulate “fungi, bacteria, and debris …” which may involve “residue from tobacco, coffee, tea, and other foods as well as porphyrin-producing chromogenic organisms in the oral flora that impart a characteristic hue,” they wrote.

BHT is diagnosed visually, often presenting with a distinctive black color, although discoloration may “range from blackish-brown to yellow-green to unpigmented,” they noted. The presence of the characteristic long, thick filiform papillae is key to differentiating BHT from other reasons for tongue discoloration, and may be confirmed microscopically.

The etiology of BHT has not been well-defined but is probably multifactorial, the authors noted, listing the following potential extrinsic and intrinsic contributors.

Extrinsic factors:

• Heavy use of tobacco, alcohol, or intravenous drugs
• Excessive consumption of coffee or black tea
• Long-term use of oxidizing/irritant mouthwash
• Recent radiation therapy to the head and neck

Intrinsic factors:

• Poor oral hygiene
• HIV
• Trigeminal neuralgia resulting in limited tongue movement
• Xerostomia

Although casual smoking poses a slightly increased risk of BHT compared to that of non-smokers (15% to 10% in men, 5.5% to 5.2% in women), heavy use of tobacco led to estimated prevalence of 58% in men and 33% in women, according to a study of various tongue lesions in 5,150 Turkish dental outpatients.

The patient reported here had insufficient saliva production as a result of her mixed connective tissue disease, and then started treatment with moxifloxacin, which led to her developing BHT. This is thought to be the first English report of moxifloxacin-induced BHT, they observed, adding that this patient’s score of 5 on the Naranjo adverse drug reaction probability scale “was higher than [that for] other drugs taken by the patient.”

While antibiotic-induced BHT is uncommon, it has been associated with use of penicillins, cephalosporins, imipenem/cilastatin, metronidazole, doxycycline, erythromycin, minocycline, and linezolid, the authors noted, citing a literature review of BHT cases from the past 20 years in which linezolid accounted for more than half of the 19 cases reported.

Theoretically, antibiotic-induced BHT occurs when “dysbiosis in the mouth gives rise to chromogenic bacteria, especially Porphyromonas gingivalis,” the group said, although fungal infections or discoloration due to antibiotic treatments themselves have also been suggested as possible causes.

Penicillin-related “inhibition of the intestinal nicotinamide-producing flora” was also included in a 1949 report, the case authors said, writing, “it is unclear if these hypotheses are adaptable to all antibiotics, because only limited antibiotics have been found causative for BHT.” Because the condition is generally self-limiting and as in this patient, rarely results in significant symptoms, “it may be underdiagnosed outside of dental clinics,” they added. Symptoms of BHT tend to improve within a few days of discontinuing likely causative agents and using good oral hygiene.