AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Mycobacterium haemophilum is a nontuberculous mycobacterium that causes skin, joint, bone, and pulmonary infections in immunocompromised persons and lymphadenitis in children. M haemophilum was first isolated from subcutaneous abscesses in a patient with Hodgkin disease. Most recent infections have occurred in patients with AIDS and in transplant recipients. 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.

Pathophysiology

The pathophysiology, natural habitat, and mechanism for acquisition of M haemophilum infection are not known. 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.

Frequency

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, Canada, Israel, United Kingdom, and South Africa.

Mortality/Morbidity

• 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.

Sex

M haemophilum infection is more common in males than in females. This may be related to the higher incidence of HIV infection in males.

Age

• Lymphadenitis occurs in young children.
• Most cases in immunocompromised patients occur in adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Lymphadenitis in children
• • 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.¹
  • Systemic symptoms are absent except for low-grade fever.
• Skin lesions
• • 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.
  • Oculofacial lesions have been reported in an immunocompetent child.²
• Septic arthritis: 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.
• Osteomyelitis
• • This is reported in patients with AIDS.
  • Skin lesions are usually present.
  • Septic arthritis is usually present.
• Pneumonia
• • 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.^{3, 4, 5}
• Central venous catheter tunnel infection: 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.⁶
• Chronic cutaneous granulomata: One case was described in a previously healthy man following a coral injury in Thailand.⁷

Physical

• Lymphadenitis
• • 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.
• Skin lesions
• • Lesions include the following:
  • • Papules
    • Subcutaneous abscesses
    • Nodules
    • Cysts
    • Scaly plaques
    • Ulcers
  • Initially, they are painless but may become painful or pruritic.
  • They may be localized on extremities over joints, or they may be diffuse.
• Septic arthritis: The major finding is a swollen fluctuant knee.
• Osteomyelitis: Septic arthritis is also present.
• Pneumonia: Fever is present.
• Central venous catheter tunnel infection: Ulcerations develop at the exit site and along the catheter track.
• Lymphadenopathy

Causes

• Risk factors for M haemophilum infection
• • HIV/AIDS
  • Immunosuppression
  • Steroid use⁸: In 30 steroid-treated mice injected with M haemophilum, 12 developed ear lesions similar to the skin lesions observed in humans; no legions developed in mice that were not treated with steroids.⁹

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Lymphadenitis in children

Acute toxoplasmosis
Actinomycosis
Epstein-Barr virus infection
Lymphoma
Tuberculosis (TB) adenitis secondary to Mycobacterium avium complex,
Mycobacterium kansasii, Mycobacterium scrofulaceum, or Mycobacterium tuberculosis infection

Skin lesions

Mycobacterium chelonae infection
Mycobacterium fortuitum infection
Mycobacterium marinum infection
Mycobacterium abscessus infection
Staphylococcal furunculosis
Vasculitis
Disseminated cryptococcal disease
Disseminated aspergillosis
Septic arthritis or osteomyelitis
Lymphoma
Bacillary angiomatosis
Bacterial osteomyelitis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Evaluate the CBC count, liver enzymes, and serum electrolyte levels, including creatinine.
• Acid-fast bacillus smear and culture
• • 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.¹⁰
  • 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.¹¹

Imaging Studies

• Radiography
• • Radiographs 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.

Other Tests

• 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.¹²

Procedures

• Aspirate of lesions may reveal AFB.

Histologic Findings

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

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• 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 development of resistance. Susceptibility testing is not standardized, but M haemophilum is usually susceptible to amikacin, ciprofloxacin, and other quinolones (eg, levofloxacin, 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:
• • Rifampin and ciprofloxacin
  • Ciprofloxacin, clarithromycin, and rifampin
  • Rifampin and minocycline
  • Clarithromycin, minocycline, and rifampin

Surgical Care

• Lymphadenitis in children: Total excision of the involved lymph node or nodes is the treatment of choice.

Consultations

• Infectious disease expert
• Pulmonologist
• Mycobacterium expert
• Health department

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Antimicrobial agents

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• 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.

Further Outpatient Care

• 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.

Prognosis

• 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.

Patient Education

• 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.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Rifampin and rifabutin may interfere with contraceptives; the patient may become pregnant.
• Ciprofloxacin, but not other quinolones, rarely cause Achilles tendon ruptures; avoid high-impact sports.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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2. Lindeboom JA, Kuijper EJ, Bruijnesteijn van Coppenraet ES, Prins JM. First case of an oculofacial lesion due to Mycobacterium haemophilum infection in an immunocompetent child. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. Jun 2006;101(6):774-6. [Medline].
3. Kiehn TE, White M. Mycobacterium haemophilum: an emerging pathogen. Eur J Clin Microbiol Infect Dis. Nov 1994;13(11):925-31. [Medline].
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16. Holladay KL, Carmichael JK. Mycobacterium haemophilum cellulitis and osteomyelitis in a man with AIDS. J Am Board Fam Pract. Mar-Apr 1996;9(2):122-4. [Medline].
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20. Samra Z, Kaufmann L, Zeharia A, Ashkenazi S, Amir J, Bahar J, et al. Optimal detection and identification of Mycobacterium haemophilum in specimens from pediatric patients with cervical lymphadenopathy. J Clin Microbiol. Mar 1999;37(3):832-4. [Medline].
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22. Straus WL, Ostroff SM, Jernigan DB, Kiehn TE, Sordillo EM, Armstrong D, et al. Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an emerging pathogen in immunocompromised patients. Ann Intern Med. Jan 15 1994;120(2):118-25. [Medline].
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Article Last Updated: Nov 20, 2007