Dermatology Online Journal

Short course of clarithromycin in an immunocompetent patient with BCG-induced regional complications
Torres-Rojas JR¹, Rondón-Lugo A², Rosa Vidal³
Dermatology Online Journal 8(2): 6

1. Instituto de Medicina Tropical and 2. Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela, and 3.Clínica Santa Sofía, Caracas; Venezuela.

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Abstract

Bacillus Calmette Guerin (BCG) has been used to vaccinate against tuberculosis since 1921. Persistant skin and lymph node lesions yielding Mycobacterium bovis are a rare complication for which there is not standardized treatment. We report an 11 month old child with a progressive cutaneous nodule and lymphadenopathy after BCG vaccination. These rapidly cleared with administration of clarithromycin.

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Bacillus Calmette Guerin (BCG) is a freeze-dried preparation made from a living culture of Calmette-Guerin attenuated strain of Mycobacterium bovis. First developed as a vaccine against tuberculosis in 1921, it has been used as an immunotherapeutic agent in the treatment of carcinoma.[1] Unfortunately, BCG vaccines used in various parts of the world differ widely in morphology, growth characteristics, sensitizing potency, and animal virulence.[1,2] Local reactivity differs between vaccines, varying with both strain and number of viable bacilli. [1,2]

BCG vaccine is extremely safe in immunocompetent hosts. Local ulceration and regional suppurative adenitis that usually resolve spontaneously may occur in 0.1-1% of those vaccinated. [1,2] M. bovis can be cultured from the skin lesions as well as from local involved lymph nodes, but acid-fast staining of histological sections often does not reveal the micorganism. [1,3] The production of local lesions does not necessarily suggest underlying host immune defects and does not affect the level of protection afforded by the vaccine. [1,3]

While anti-tuberculous chemotherapy is currently recommended for persistent local lesions, the efficacy of this therapy remains to be established. [1,3,4] We herein comment on our experience with a recent case of BCG-induced local chancre and lymphadenitis successfully treated with a short course of oral clarithromycin.

Case Report

An 11 month-old immunocompetent girl presented with a chronic cutaneous chancre and lymphadenopathy involving multiple cervical and supraclavicular lymph nodes which appeared 6 months after local intradermal inoculation with BCG vaccine. She had been sick for 5 months and had received various unsuccessful courses of treatment with oral cephalosporins, amoxicillin and azithromycin.

Physical examination showed an otherwise healthy looking child. An ulcerated erythematous, non-tender, cutaneous nodule, approximately 3 x 2 cm in diameter, was visible on her left lower deltoid region (Figure 1). The ulcer was shallow and sharply demarcated with infiltrated borders. It was covered by a serous crust, which after cleaning, revealed a granulous, oozing, base. Several enlarged, non-tender, non-adherent, ipsilateral cervical and supraclavicular lymph nodes were noticed. General clinical laboratory results were not contributory. A gram stain of the inflammatory drainage revealed only abundant polymorphonuclear leukocytes, but no bacteria. Acid fast stains were negative. A slowly growing mycobacteria was isolated after one month, which was later identified as Mycobacterium bovis.

Figure 1
Figure 1: Ulcerated, 3 x 2 cm in diameter, erythematous, cutaneous nodule. Note the sharply infiltrated free borders and the yellowish inflammatory drainage

The patient was started on chlarithromycin, 7.5 mg/kg/day, orally. Progressive healing of the lesion was noticed over 15 days. The antibiotic was stopped after a total of 21 days. No relapses have been observed after 8 months of follow up.

Discussion

In about 90-95% of vaccine recipients, BCG causes a specific lesion that starts as a papule two or more weeks after vaccination. This then becomes ulcerated and heals after several weeks, leaving a scar. Although unusual, other diverse untoward effects have been associated with the inoculation of BCG. They include: osteomyelitis, arthritis and other bones complications, lupus vulgaris, sarcoidosis, cold abscesses, hepatitis, optical neuritis, scars and pitiriasis. [1,2,3] Inadvertent revaccination may seldom cause necrotizing cerebral arteritis and meningitis in previously healthy immunocompetent children. [1,2,3,5]

In the immunocompromised host, lymphadenitis, osteitis and generalized infection can appear after BCG inoculation. The frequency of lymphadenitis attributed to BCG appears similar both in newborn children infected with HIV-1 and in non-infected children. [1,2,6]

Some authors recommend systemic treatment of severe persistent lesions with oral isoniazid. [1,2,4] However, lesions may persist long after initiation of therapy, and placebo controlled trials of treatment are still needed. [1,2,4]

Recent data indicate that BCG strains of M. bovis are usually susceptible, in vitro, to all the tuberculostatic drugs, except for pyrazinamide and cycloserine. They are also susceptible to fluoroquinolones and some ketolides, but resistant to beta-lactams, macrolides (except clarithromycin, which consistently exhibits MICs (1.25 mcg/ml), and some aminoglycosides.[7,8]

Clarithromycin has been successfully used as a fifth antituberculous agent in a patient with X-linked severe combined immunodeficiency who developed disseminated BCG infection following bone marrow transplantation. [9] We are not aware of previous experience with clarithromycin as monotherapy in the treatment of local BCG complications.

A short course of oral clarithromycin alone may prove an attractive alternative to conventional combined antituberculous schedules, in immunocompetent children with local BCG-induced complications.

References

1. Grange JM. Complications of bacille Calmette-Guèrin (BCG) vaccination and immunotherapy and their management. Communicable Dis Pub Health 1998; 1: 84-8.

2. Milstien JB, Gibson JJ. Quality control of BCG vaccine by World Health Organization: A review of factors that may influence vaccine effectiveness and safety. Bull World Health Organ 1990;68(1):93-108.

3. Williams DE. Mycobacterium bovis BCG infection in humans. In: Thoen CO, Steele JH, editors. Mycobacterium bovis infection in animals and humans. Ames: Iowa State University Press, 1995: 47-61.

4. Hanley SP, Gumb J, MacFarlane JT. Comparison of erythromycin and isoniazid in treatment of adverse reactions to BCG vaccination. BMJ 1985; 290: 970.

5. Tardieu M, Truffot-Pernot C, Carriere JP, Dupic Y, Landrieu P. Tuberculous meningitis due to BCG in two previously healthy children. Lancet 1988;1:440-441.

6. Lallemant-Le Coeur S, Lallemant M, Cheynier D, Nzingoula S, Drucker J, Larouze B. Bacillus Calmette-Guerin immunization in infants born to HIV-1-seropositive mothers. AIDS 1991;5(2):195-199.

7. Durek C, Rüsch-Gerdes S, Jocham D, Böhle A. Sensitivity of BCG to modern antibiotics. Eur Urol 2000 37 Suppl 1:21-5

8. Rastogi N, Goh KS, Berchel M, Bryskier A. In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4. Antimicrob Agents Chemother 2000, 44: 2848-52

9. McKenzie RH, Roux P. Disseminated BCG infection following bone marrow transplantation for X-linked severe combined immunodeficiency. Pediatr Dermatol 2000, 17:208-12

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