Mycobacterium haemophilum is a nontuberculous mycobacterium that causes skin, joint, bone, and pulmonary infections in immunocompromised persons and lymphadenitis in children.[1, 2]
M haemophilum was first isolated from subcutaneous abscesses in a patient with Hodgkin disease. Most recent infections have occurred in patients with AIDS, in transplant recipients, and in patients receiving tumor necrosis factor-alpha inhibitors.[3, 4, 5] M haemophilum skin infection has been associated with permanent eyebrow makeup and tattoos,[6] as well as acupuncture treatments.[7]
M haemophilum is a fastidious (requires special growth media) mycobacterium that requires heme-supplemented culture media and low temperatures for growth. Because of these features, it is probably underdiagnosed.
The pathophysiology, natural habitat, and mechanism for acquisition of M haemophilum infection are not known. Water reservoirs may be the source of M haemophilum infections. Immunocompromised adults with M haemophilum infection most commonly present with skin lesions. Septic arthritis and osteomyelitis may also occur. Pulmonary infection is much less common and may follow skin disease. M haemophilum infection occasionally causes pulmonary infection initially. Mycobacteremia may occur.
United States
More than 40 cases of M haemophilum infection have been reported, including 10 cases in Arizona from 1984-1994. Most cases occurred in immunosuppressed patients. The incidence of disease is unknown.
International
Cases of M haemophilum infection have been reported sporadically from Australia, France, Germany,[8] Canada, Israel, United Kingdom, and South Africa.
In healthy children, localized cervical lymphadenopathy is a benign disease that responds well to excision of the involved lymph nodes.
In immunocompromised patients, the outcome of disease is determined by the degree of underlying immunosuppression. Some patients with AIDS respond to therapy, while others respond initially but relapse later. Fatalities have occurred in bone marrow transplant recipients.
M haemophilum infection is more common in males than in females. This may be related to the higher incidence of HIV infection in males.
Lymphadenitis occurs in young children.
Most cases in immunocompromised patients occur in adults.
Prognosis for children with localized lymphadenitis is good.
In adults, the outcome is determined by their immune function.
In severely immunosuppressed patients, disease may require long-term therapy. Despite maintenance therapy, infection may persist or recur.
Adherence to medication is of utmost importance to prevent resistance.
Instruct patients to list all medications to avoid drug interactions.
Rifampin and rifabutin may interfere with contraceptives and numerous other medications, especially HIV-related therapy.
The most common symptom is swelling of the neck, which slowly enlarges over several weeks to months. The enlarged nodes may be painful. A course of antimicrobial therapy (eg, 2 wk of oral amoxicillin/clavulanic acid) does not cure the swelling.
Inguinal lymphadenitis has also been reported.[9]
Systemic symptoms are absent except for low-grade fever.
Six cases have occurred in immunocompetent adults.[10]
Cervicofacial lymphadenitis has been reported in immunocompromised adults.[11]
Skin lesions are the most common presenting symptom in immunosuppressed patients.
Lesions usually develop on the extremities over joints. They may begin as papules, subcutaneous nodules, scales, or cysts and are initially painless but often become tender and pruritic. Painful ulcerations may occur. Erythema may surround the lesion.
Lesions may resemble sporotrichosis.[12]
Oculofacial lesions have been reported in an immunocompetent child.[13]
Erythematous plaques and subcutaneous nodules of the face mimicking leprosy have been reported.[14, 15]
Nodular skin lesions have occurred after permanent tattooing of eyebrows in 2 women.[16]
Tattoo-associated skin lesions have occurred in immunocompetent adults[17]
Skin lesions have been reported prior to onset of B cell lymphoma in a liver transplant recipient.[18]
Patients present with pain and swelling over a joint, usually the knee or elbow. Often, the patient has a history of cutaneous lesions overlying the joint.[19]
This has been reported in a renal transplant recipient.[20]
This is reported in patients with AIDS.
Skin lesions are usually present.
Septic arthritis is usually present.
Symptoms include fever, cough, pleuritic chest pain, and dyspnea.
Patients may have a history of treated cutaneous lesions.
This is reported in bone marrow transplant recipients and patients with AIDS.[21, 22, 23]
Two cases in immunosuppressed patients have been reported. The first patient presented with a supraclavicular mass with overlying cellulitis that progressed to ulceration. The second patient had an ulceration and purulent discharge at the former site of a Hickman catheter.[24]
One case was described in a previously healthy man following a coral injury in Thailand.[25]
This has been reported in a cardiac transplant patient.[26]
This has been reported in a renal transplant patient.[27]
This has been reported in patients with AIDS.[28, 29]
The submandibular and cervical nodes are most frequently involved. Perihilar nodes are involved less frequently. Enlarged nodes are usually unilateral and may be tender and fluctuant. Overlying skin may be erythematous.
Low-grade fever may be present.
Lesions include the following:
Initially, they are painless but may become painful or pruritic.
They may be localized on extremities over joints, or they may be diffuse.
The major finding is a swollen fluctuant knee.
Septic arthritis is also present.
Fever is present.
Ulcerations develop at the exit site and along the catheter track.
Lymphadenopathy may occur.
Risk factors for M haemophilum infection include the following:
Evaluate the CBC count, liver enzymes, and serum electrolyte levels, including creatinine.
M haemophilum is a slow-growing, acid-fast–positive, nontuberculous mycobacterium that requires media supplemented with ferric iron–containing compounds and grows best at 30-32°C. Growth on solid media usually takes 2-3 weeks. The organism typically does not stain with Gram stain.
Aspirate of lesions may reveal acid-fast bacilli.
Perform an acid-fast bacillus (AFB) smear on excised lymph nodes. Culture a specimen at 30-32°C in media supplemented with iron or heme.
In patients with septic arthritis and osteomyelitis, submit synovial fluid specimens and bone biopsy samples for AFB smear and culture. Synovial fluid is usually purulent, and M haemophilum may be isolated from the fluid.
Submit sputum from immunosuppressed patients with pneumonia for AFB smear and culture. M haemophilum can be cultured from the blood of some patients with AIDS using special isolator tubes.
In appropriate clinical settings (eg, skin lesions, lymphadenopathy), informing the mycobacteriology laboratory to culture for M haemophilum may be useful. Iron must be added to grow this organism.
M haemophilum is unlikely to be a saprophyte (an innocent bystander) or a laboratory contaminant in the appropriate clinical setting.
Polymerase chain reaction (PCR)–restriction endonuclease analysis has been used for direct identification of M haemophilum in clinical specimens from immunocompromised patients.[37, 38, 39, 40]
M haemophilum –specific PCR has been used to diagnosis M haemophilum cervicofacial lymphadenitis in children and was superior to culture in one series of patients from the Netherlands.[41]
Radiography of involved joints or bone may demonstrate soft tissue swelling and lytic lesions. Chest radiograph findings are abnormal in patients with pneumonia. Unilateral or bilateral infiltrates may appear.
CT scans of the chest may reveal abnormalities that are not revealed with chest radiography. Regular cuts of 5-7 mm should be sufficient; high-resolution CT scan is rarely necessary.
MRI demonstrates medullary lesions and cortical disruption.
Diagnosis has been made using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scanning.[42]
In children with lymphadenitis a tuberculin skin test result with purified protein derivative (PPD) of tuberculosis may be positive; however, it is rarely larger than 9 mm.[43]
Biopsy specimens of skin lesions show granulomatous panniculitis and caseating or noncaseating granulomas. Patients with AIDS have poorly formed granulomas. A neutrophilic infiltrate with multinucleated giant cells may be observed. AFB smear results are usually positive, revealing large, pleomorphic, or curved AFB.
Lymph node biopsy may reveal granulomas, necrosis, granulating tissue, or multinucleated giant cells, and the specimen may be smear-positive for AFB.
Treatment is determined by the degree of immunosuppression. In healthy children with lymphadenitis, surgical excision is the preferred treatment. In immunosuppressed patients, reversal of immunosuppression is the most effective treatment. Immunosuppressed patients require combination therapy to prevent the development of resistance. Susceptibility testing is not standardized, but M haemophilum is usually susceptible to amikacin, ciprofloxacin, and other quinolones (eg, levofloxacin, moxifloxacin), clarithromycin, rifabutin, rifampin. M haemophilum is usually resistant to ethambutol, ethionamide, isoniazid, and streptomycin. Although the optimal regimen is not known, combinations have had some clinical success.
Effective drug combinations include the following:
Lymphadenitis in children: Total excision of the involved lymph node or nodes is the treatment of choice.[44]
See the list below:
Patients require close outpatient follow-up care to document response to therapy (eg, every 2-4 wk). Length of therapy is prolonged in immunosuppressed patients, and patients with irreversible immunosuppression may require life-long suppressive therapy. Relapses have occurred in patients with AIDS who were on suppressive therapy. Whether patients on highly active antiretroviral therapy (HAART) can stop therapy if they have a good HAART response is unknown.
Discuss adherence to medications extensively with the patient to avoid development of resistance.
M haemophilum infection is diagnosed in many immunosuppressed patients who are hospitalized.
Treatment can be started or continued on an outpatient basis in most patients.
Although no standardized treatment exists, a regimen that includes a combination of at least 2 drugs with low minimum inhibitory concentrations (MICs) against M haemophilum is preferred.
A 3-drug combination of ciprofloxacin, clarithromycin, and rifampin or rifabutin has been used for cutaneous disease in bone marrow transplant recipients. No standard treatment exists; optimal treatment time is unknown.
Clinical Context: Macrolide with activity against various nontuberculous mycobacteria. Binds to bacterial 50S ribosomal subunit and inhibits RNA-dependent protein synthesis.
Clinical Context: Important drug used in the treatment of infection with M tuberculosis and nontuberculous mycobacterial infections. Inhibits DNA-dependent RNA polymerase activity.
Clinical Context: Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth. Other quinolones such as levofloxacin, sparfloxacin, and ofloxacin may also be effective.
Clinical Context: Expected to be a powerful drug for mycobacteremia. Starting amikacin may be beneficial at least as long as the patient is septic.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.