Mycobacterium haemophilum in a patient with inflammatory bowel disease

Clinical record

A 38‐year‐old woman with longstanding Crohn’s disease presented with 7 months of a non‐healing widespread rash. Examination revealed indurated and ulcerated papulonodular lesions on the abdomen and extremities (Box 1). Medications included adalimumab, 6‐mercaptopurine, allopurinol and an oral contraceptive pill. There were no other significant medical conditions. The main differentials considered were cutaneous/metastatic Crohn’s disease or a disseminated atypical infection such as atypical mycobacterium or deep fungal. The lesions were too numerous for a skin malignancy.

Incisional biopsy samples with her initial dermatologist revealed small non‐necrotising granulomas. Special stains such as periodic acid–Schiff, Wade–Fite and Ziehl–Neelsen sections were negative for fungi and acid‐fast bacilli. Biopsy culture was negative after one week incubating at 35°C in the standard media. All other investigations were normal or negative.

Given the clinical and histopathological features combined with negative special stains and cultures, the diagnosis of cutaneous Crohn’s disease was favoured. This resulted in the decision to increase the dose of adalimumab and institute both topical and intralesional steroids.

Treatment with topical betamethasone dipropionate 0.05% ointment and intralesional triamcinolone 10mg/mL with her initial dermatologist and subsequent doubling of the adalimumab dose from 40mg fortnightly to weekly under the guidance of her gastroenterologist had no benefit over 6weeks.

In view of the clinical picture and lack of response to treatment, the patient was urgently referred to our dermatology department where we reinvestigated for an infectious aetiology.

Haematoxylin–eosin stains showed a complex pattern of inflammation with superficial ulceration (Box 2). There were poorly formed granulomas which were not as small and discrete as typically seen in Crohn’s disease. Plasma cells were present but no eosinophils. Special stains (periodic acid–Schiff and Ziehl–Neelsen) did not find any fungi or acid‐fast bacilli. Culture swabs grew sensitive Staphylococcus aureus. Oral cephalexin provided no benefit. No further treatment was given pending the results of repeat cultures.

After 6 weeks of incubation at 32C° and 35°C, Mycobacterium haemophilum was isolated. Her Crohn’s disease was in remission with adalimumab, 6‐mercaptopurine and allopurinol, and all were ceased when the mycobacteria were cultured.

A computed tomography scan of the chest, abdomen and pelvis showed no systemic involvement. Treatment was instituted with 6 months of oral ciprofloxacin 500mg, rifampicin 300mg and clarithromycin 500mg under the guidance of the infectious diseases team.

After 8 weeks, the lesions improved and her Crohn’s disease remained in remission. The patient became pregnant 4 weeks later and, after discussion, she ceased all antibiotics. She remains systemically well. Antibiotics will be recommenced after delivery.

Discussion

Mycobacterium haemophilum is a non‐tuberculous, slow growing acid‐fast bacillus and an increasingly recognised pathogen in immunocompromised patients.1 The organism is found in the environment, especially water reservoirs, and has been associated with tattoo parlours and acupuncture needles.2 Cutaneous M. haemophilum typically presents as multiple tender violaceous nodules on extremities which develop into abscesses or ulcers.1 Systemic involvement includes arthritis, lymphadenitis, and disseminated and pulmonary infections. Its occurrence on extremities is likely due to its preference for lower temperatures of 30–32°C.2

M. haemophilum is a slow growing organism needing up to 8 weeks of incubation, making diagnosis difficult.2,3 Methods of rapid species identification include DNA sequencing or polymerase chain reaction (PCR).4 Although pan‐mycobacterial PCR panels are available in Australia, and can be diagnostically helpful, in the presence of a low mycobacterial load, false negative results are possible and therefore cannot be a substitute for culture.4

M. haemophilum infection can be difficult to differentiate from cutaneous Crohn’s disease clinically and histologically (Box 3).5,6

The likelihood of detection of M. haemophilum in biopsy samples is increased by shorter laboratory transit time, using liquid media and specific mediums, such as an iron source, and lower incubation temperature at 30°C.4

Tumour necrosis factor (TNF)‐α has a critical role against Mycobacterium infection through T helper cell 1 based cell‐mediated immune response.7 Adalimumab is a TNF‐α inhibitor used in the treatment of inflammatory bowel disease, hidradenitis suppuritiva and other conditions.8 Granulomatous infections in patients receiving adalimumab are well recognised complications, as reflected by the increasing number of cutaneous M. haemophilum infections in patients receiving adalimumab and other TNF‐α inhibitors.3,9,10

Repeat cultures were likely positive because they were performed after intralesional steroids and higher doses of adalimumab. Greater immunosuppression decreases local inhibition of mycobacterial growth. The diagnosis of atypical infections can be difficult with false negative results on histopathology and culture. Empirical treatment of granulomatous skin disease in immunocompromised patients should be avoided.

The consensus for treatment of M. haemophilum is a combination of clarithromycin, ciprofloxacin and rifampicin.2 Ciprofloxacin and clarithromycin are both pregnancy Category B drugs. Rifampicin is Category C but has been used widely to treat tuberculosis during pregnancy.11

Maternal–fetal complications in Crohn’s disease are related to the activity of the disease at time of conception.8 Most Crohn’s disease medications can be continued during pregnancy, except for methotrexate and thalidomide.8

Box 1 – Left forearm and left leg of patient at initial presentation

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Box 2 – Biopsy sample from patient’s left wrist (haematoxylin–eosin stain)

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A: A superficial to deep inflammatory infiltrate is dense in the top dermal half (arrows) (magnification ×40). B: Poorly demarcated granulomatous focus with scattered Langerhan multinucleate giant cells (arrows) (magnification ×100). C: A small, better formed granuloma can be seen in the mid top third of the image (red arrow); plasma cells are shown in the bottom right field (yellow arrow) (magnification ×100). D: Inflammatory infiltrate at the dermo‐epidermal junction (magnification ×100).