Disseminated Mycobacterium chelonae Infection in a Patient Receiving an Epidermal Growth Factor Receptor Inhibitor for Advanced Head and Neck Cancer

Abstract

We report a case of disseminated cutaneous Mycobacterium chelonae infection in a patient with head and neck cancer on salvage chemotherapy, including the epidermal growth factor receptor inhibitor cetuximab. Mycobacterium chelonae should be considered in the differential diagnosis of cutaneous infections in cancer patients receiving epidermal growth factor receptor inhibitors.

CASE REPORT

A 64-year-old woman with a history of squamous cell carcinoma (SCC) of the mouth presented with a 1-week history of fever, fatigue, and rash. She was diagnosed with SCC 6 years previously, when staging revealed T4N1 disease of the right alveolar ridge with extension into the mandible, floor of the mouth bilaterally, and buccal mucosa. She underwent chemotherapy, radiation, and surgical resection. Five years later, she had recurrence of the SCC, requiring a left hemilaryngectomy and selective neck dissection. Pathology revealed poorly differentiated invasive SCC. Given the extent of recurrence, as well as severe fibrotic changes from her previous treatment, the patient was not a candidate for reirradiation. She had been treated for approximately 9 months with a palliative chemotherapy regimen that included carboplatin and gemcitabine, with the last cycle 3 weeks prior to presentation. In addition to this, she received weekly cetuximab for the past 9 months. She completed her last dose 1 week prior to hospitalization. Other medications included dexamethasone at 4 mg daily and minocycline at 50 mg twice daily.

On examination, the patient was febrile to 39.1°C and hypoxic. She had crackles on lung examination, and skin exam revealed multiple nontender erythematous nodules on her legs (Fig. 1), as well as a tender 2-cm furuncle on her right hand and a 5- by 6-cm erythematous purpuric patch on her right leg. A complete blood count showed a white blood cell count of 3,400 cells/mm³ with 82% neutrophils, hemoglobin of 7.5 g/dl, and a platelet count of 47,000/mm³. Chest computed tomography (CT) revealed bilateral pulmonary infiltrates. She was treated with vancomycin and piperacillin-tazobactam for suspected pneumonia, as well as bacterial soft tissue infection. The lesion over her right hand was drained, and culture grew methicillin-susceptible Staphylococcus aureus. Given the unusual appearance of her leg lesions, a biopsy was performed. The histopathology showed a dense infiltrate of neutrophils within the superficial and deep reticular dermis extending into the subcutaneous fat, and a Kinyoun's stain was positive for acid-fast bacilli (AFB) (Fig. 2). One set of conventional blood cultures from admission grew AFB at day 5 of incubation, and clarithromycin and imipenem-cilastin were started. The skin biopsy specimen culture also grew AFB that, along with the blood isolate, were later identified as Mycobacterium chelonae by PCR amplification and restriction endonuclease fragment analysis of the 65-kDa heat shock protein gene sequence, as previously described (10). The isolate was susceptible in vitro to clarithromycin and tobramycin and resistant to amikacin, cefoxitin, ciprofloxacin, doxycycline, imipenem, and trimethoprim-sulfamethoxazole (identification and susceptibility testing were performed by Richard Wallace at the University of Texas Health Center at Tyler). Over the following week, the patient's respiratory status and skin lesions both improved. She was discharged to a skilled nursing facility for physical rehabilitation. She was transferred back to another hospital 2 days later because of shortness of breath and chest pain. Physical examination revealed enlarged neck lesions, and diagnostic imaging showed a large left pleural effusion. A biopsy specimen of the neck lesions again revealed SCC. She elected not to undergo further treatment and was discharged with hospice care.

Fig 1.

Nodular lesions on the patient's knee.

Fig 2.

Hematoxylin and eosin stain of the skin biopsy section. Original magnification, ×40. The inset shows the Kinyoun stain with acid-fast bacilli. Original magnification, ×1,000.

Mycobacterium chelonae is a species of rapidly growing mycobacterium belonging to the M. chelonae-abscessus group, which also includes Mycobacterium abscessus and Mycobacterium immunogenum (3). The most common clinical manifestations of M. chelonae infection are cutaneous lesions. Wallace et al. described three major types of clinical cutaneous presentation: disseminated cutaneous disease (most common); localized cellulitis, abscess, or osteomyelitis; and catheter-associated infections. Corticosteroid use and previous skin trauma have been identified as major risk factors for cutaneous disease due to M. chelonae (12).

The current case describes an immunocompromised cancer patient with disseminated M. chelonae infection after receiving cytotoxic chemotherapy and cetuximab for advanced head and neck cancer. Cetuximab is an epidermal growth factor receptor (EGFR) monoclonal chimeric immunoglobulin G1 antibody approved for the treatment of colorectal cancer and head and neck cancer. It has been shown to improve survival in patients with advanced forms of these cancers (2, 7, 11). Inherent to the inhibition of EGFR is skin toxicity, which presents as a papulo-pustular rash in the majority of patients. In fact, both the presence and severity of rash have been shown to be positively associated with tumor response and survival (4, 8). Infections are also associated with this skin toxicity. Eilers et al. found that nearly 40% of patients with skin toxicity on EGFR inhibitors developed dermatologic infections (6). The most common pathogen reported was S. aureus, and there were no mycobacterial infections in that series.

This is the first report of disseminated infection due to a rapidly growing mycobacterium in a patient treated with an EGFR inhibitor. M. chelonae infection has been described with the use of adalimumab, an anti-tumor necrosis factor monoclonal antibody (5). While our patient had multiple known risk factors for the development of M. chelonae infection, cetuximab-associated skin toxicity may have been a contributing factor, especially since skin trauma is a major risk factor for cutaneous disease due to M. chelonae. Alternatively, other mechanisms may have played a role in increasing our patient's susceptibility to M. chelonae infection. Bermudez et al. reported the existence of an EGFR-like receptor on M. tuberculosis and Mycobacterium avium, as well as enhanced mycobacterial growth in the presence of epidermal growth factor (1). In addition, Matsuo et al. found that cetuximab itself induced phosphorylation in the absence of growth factors (9). It is theoretically possible that cetuximab binding could facilitate mycobacterial proliferation, but we have no evidence to suggest that this was the case in our patient. In conclusion, rapidly growing mycobacteria should be considered in the differential diagnosis of dermatologic infections in patients receiving EGFR inhibitors.