1 INTRODUCTION

Linezolid is an oxazolidinone group of antimicrobial agent. It has been widely used for methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). It is also found much useful in uncomplicated skin and soft tissue infections. The commonside effects were headache, nausea, vomiting, and diarrhea; however, patients who received the antibiotic for more than 2 weeks were reported with thrombocytopenia, neuropathies, anemia, and reversible bone marrow suppression.1, 2

Linezolid usage is also associated with a rare adverse event of either blackish discoloration or hypertrophy and pigmentation of the filiform papillae, commonly known as “black hairy tongue.”3 The other commonest causes of the discoloration of the tongue and the oral mucosa are metabolic disorders, physiological, and toxic metabolites.4 Only 0.2% of the patients receiving linezolid therapy were found with the incidence of black hairy tongue.5 Ruling out the other possible causes of the black hairy tongue, it is found that linezolid will be the exclusive cause of this episode in this patient. Hence it is found worth reporting this incident.

2 CASE REPORT

A 65-year-old male, presented to the outpatient Department of General medicine at Meenakshi Medical College Hospital & Research Institute, Kanchipuram with symptomatic black hairy tongue on seventh day after taking linezolid 600 mg twice daily for his left diabetic foot ulcer. He is a known type 2 diabetic patient on regular treatment with oral hypoglycemic agent for the past 12 years, has developed diabetic foot ulcer measuring 5 × 6 × 2 cm involving the sole of the right foot for the past 6 months and was classified as grade 2 according to the Wagner's classification. He was prescribed linezolid 600 mg, 12 h once based on the pus culture from the wound, which was found to be MRSA strain and sensitive to linezolid.

On examination of his oral cavity, dark brownish discoloration was seen on the posterior aspect of the dorsum of the tongue tailing towards the anterior aspect sparing tip and the sides (Figure 1). There was mild foreign body sensation while swallowing and mild loss of taste sensation. He was much concerned about the recent tongue discoloration; otherwise the oral hygiene of the patient was good. He is not a known case of smoker, alcoholic or a beetle chewer. There were no associated skin rashes or regional cervical lymph node enlargement. Rest of the systemic examination was uneventful.

Black hairy tongue after receiving linezolid for 7 days

Laboratory investigations revealed: WBC 7000/μl (4000–10 000/μl), hemoglobin 10.6 g/dl, platelets 50 000/μl (150000–400 000/μl), no growth on the blood culture. There was consistent report of thrombocytopenia detected from the fifth day of the therapy.

The antibiotic use was recent and coinciding with the appearance of the black hairy tongue. Review of literature was started to find the relation between hairy tongue and linezolid usage. Literature showed the clear correlation of previous reports of hairy tongue as an adverse event in linezolid therapy.

2.1 Patient consent

The purpose of reporting this incident was explained to the patient and his written informed consent for publication of the case report and the images was obtained prior.

Wagner Scale.6

Grade 0: no open lesions, may have healed lesions.

Grade 1: superficial ulcer, no penetration in deeper layers.

Grade 2: deeper ulcer reaching tendon, bone, or joint.

Grade 3: deeper tissues are involved, with abscess, osteomyelitis, or tendonitis.

Grade 4: gangrene of some part of the foot.

3 DISCUSSION

Black hairy tongue (BHT) is characterized by elongated and hypertrophied filiform papillae with brownish black discoloration on the posterior dorsum of tongue, which is usually benign and self-limiting. Black hairy tongue is usually asymptomatic, rarely presents with dysgeusia, halitosis, nausea, and tickling of the tongue.7 General predisposing factors for BHT are chewing and smoking tobacco, xerostomia, substance abuse like cocaine, poor oral hygiene, using peroxide containing mouth washes and drugs like steroids, bismuth, methyldopa, tetracycline, etc.8

Linezolid is an effective oxazolidinone group of antibiotic. Since its use is highly active against methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) its use in the community has increased tremendously.9 With the commonest existing side effects like headache, nausea, and vomiting, usage of linezolid for more than 2 weeks has shown to cause thrombocytopenia, anemia, neuropathies, and bone marrow suppression, which is reversible when the drug is discontinued.9, 10 Reports of black hairy tongue caused by linezolid therapy in south Indians is found very uncommon. In this clinical report, we enclose a rare entity called as lingua villosa nigra (black hairy tongue) in a 65-year-old diabetic male receiving linezolid therapy. The adverse drug reaction probability was assessed using Naranjo's adverse drug reaction probability scale (NADRPS) (Table 1). In this report the linezolid-induced BHT score was found to be 6/10.

TABLE 1. Naranjo's algorithm Questions Score 1. Are there previous conclusive reports on this reaction? 1 2. Did the adverse event appear after the suspected drug was administered? 2 3. Did the adverse drug reaction improve when the drug was discontinued or a specific antagonist was administered? 1 4. Did the adverse reaction reappear when the drug was readministered? 0 5. Are there alternative causes (other than the drug) that could on their own have caused the reaction? 2 6. Did the reaction reappear when the placebo was given? 0 7. Was the drug detected in the blood (or other fluids) in concentrations known to be toxic? 0 8. Was the reaction more severe when the dose was increased or less severe when the dose was decreased? 0 9. Did the patient have a similar reaction to the same or any similar drugs in any previous exposure? 0 10. Was the adverse event confirmed by any objective evidence? 0 Total score 06

Based upon the above criteria, our total score was 6 (i.e., probable) according to the Narinjo's algorithm, which clearly indicates that linezolid therapy may be a probable cause for BHT. Withdrawal of the offending drug showed complete resolution of the black hairy tongue (Figure 2).

Complete resolution of black hairy tongue after the drug withdrawal

4 CONCLUSION

Linezolid induced black hairy tongue is a benign and self-limiting condition. To avoid the occurrence of the condition it is always advised to maintain a good oral hygiene and by avoiding the concomitant risk factors like smoking and rinsing the mouth with warm water after consumption of coffee, green tea or other colored beverages. This reaction has been reported to create awareness on the adverse reaction of linezolid and to reduce the anxiety on the reaction among the treating physicians about the rare side effect of this medication.

ACKNOWLEDGEMENT

The authors thank the Dean, Teaching, and Non-teaching staff of the Meenakshi Medical College and Research Institute for the help and support of our study.

CONFLICT OF INTEREST

There are no conflicts of interest.

AUTHOR CONTRIBUTIONS

Clinical Observation: SS, GGR; Design of the Work: SS; Literature Collection: RM; Preparation of Manuscript: SS, BVC; Data Analysis: GGR, BVC.

ETHICS STATEMENT

The study was approved by the Meenakshi Medical College Hospital and Research Ethics Committee, the patient gave written informed consent.

REFERENCES

1Jover-Diaz F, Cuadrado-Paster JM, Talents-Bolos A, Martin-Gonzalez C. Black tongue associated with linezolid. Am J Ther. 2010; 17(4): 115- 117. 2Amir KA, Bobba RK, Clarke B, et al. Tongue discoloration in an elderly kidney transplant recipient: treatment-related adverse event? Am J Geriatr Pharmacother. 2006; 4(3): 260- 263. 3IIkay B, Efsan Y, Mehmet D. Black hairy tongue: a rare side effect of linezolid. Our Dermatology Online. 2012; 3(2): 136- 137. https://doi.org/10.7241/ourd.20122.30 4Gerson SL, Kaplan SL, Bruss JB, et al. Hematologic effects of linezolid: summary of clinical experience. Antimicrob Agents Chemother. 2002; 46(8): 2723- 2726. 5Hau T. Efficacy and safety of linezolid in the treatment of skin and soft tissue infections. Eur J Clin Microbiol Infect Dis. 2002; 21: 491- 498. 6Evaluation of the diabetic foot according to Wagner's classification in a rural teaching hospital Br J Diab & Vasc Dis 2011; 11: 74- 79. http://dvd.sagepub.com/content/11/2/74.refs.html 7Thompson DF, Kessler TL. Drug-induced black hairy tongue. Pharmacotherapy. 2010; 30: 585- 593. 8Sarti GM, Haddy RI, Schaffer D, Kihm J. Black hairy tongue. Am Fam Physician. 1990; 41: 1751- 1755. 9Jover-Diaz F, Cuadrado-Paster JM, Talents-Bolos A, Martin-Gonzalez C. Black tongue associated with linezolid. Am J Ther. 2010; 17(4): 115- 117. 10Amir KA, Bobba RK, Clarke B, et al. Tongue discoloration in an elderly kidney transplant recipient: treatment-related adverse event? Am J Geriatr Pharmacother. 2006; 4(3): 260- 263.