Letters to the Editor Rifampin Hypersensitivity in a 2-year-old Child With Successful Rapid Oral Desensitization To the Editors: anagement of tuberculosis is complicated by rising rates of drugresistant disease for which there are limited therapeutic options.1 Rifampin is the only agent recommended for prophylaxis of isoniazid-resistant, rifampin-sensitive latent tuberculosis infection.2 We describe a child latently infected after household exposure to isoniazid-resistant tuberculosis who developed facial angioedema and pruritic rash within 30 minutes after ingesting the 5th dose of rifampin. Oral antihistamine was administered and symptoms resolved over 2 hours. Rifampin was discontinued. The child was assessed in a tertiary pediatric allergy clinic. Type I hypersensitivity to rifampin was ascertained based on the clinical history and confirmed with epicutaneous and intradermal testing (Table, Supplemental Digital Content 1, http://links.lww.com/ INF/B831). The rifampin concentrations used for testing was based on a previously published report of nonirritant concentration of rifampin.3 Rapid desensitization to oral rifampin was performed and adapted from an accepted penicillin desensitization protocol.4 No premedication (antihistamine or corticosteroid) was administered. Incremental doses were administered orally every 15 minutes over a period of 3.25 hours on an inpatient pediatric ward (Table, Supplemental Digital Content 2, http://links. lww.com/INF/B832). The child continued with rifampin twice daily and completed a 3.5-month course of rifampin prophylaxis without adverse reactions before travel out of country. Adverse reactions to rifampin include fever, rash, flu-like syndrome, acute renal failure, hemolytic anemia, thrombocytopenia and anaphylaxis.5 Only a limited number of these effects are because of type 1 hypersensitivity or would be expected to respond to desensitization. Drug desensitization modifies a patient’s response to a drug that allows the patient to tolerate the drug for a
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The authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0787 DOI: 10.1097/INF.0000000000000295
temporary period in order for treatment to occur and lasts only for the duration of the treatment period. If the drug is discontinued and required in the future, the desensitization procedure must be repeated. The decision to pursue drug desensitization requires a high likelihood of drug allergy, a documented medical need for the drug, a lack of alternative agents and the benefits of drug desensitization outweigh the potential risks. Contraindications to desensitization include Steven-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms, interstitial nephritis, hepatitis and hemolytic anemia.4 Our case highlights a rare case of rifampin hypersensitivity in a young child complicated by a lack of prophylaxis alternatives given the isoniazid-resistant strain of tuberculosis and crossreactivity among rifamycins.5 Rifampin desensitization protocols previously reported occurred mainly in adults involved premedication and were conducted in the intensive care unit. Premedication with antihistamine or corticosteroids was not used as these medications do not prevent IgE-mediated reactions and have the potential to mask early IgE symptoms at lower doses of the drug, thereby risking more serious reactions at higher doses. Drug desensitization should be performed under the guidance of an Allergy specialist, or at a minimum, a physician capable of treating anaphylaxis. The protocol outlined here may be a useful tool for other practitioners, particularly in areas where tuberculosis is endemic and treatment is essential.
3. Buergin S, Scherer K, Häusermann P, et al. Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance. Int Arch Allergy Immunol. 2006;140:20–26. 4. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259–273. 5. Antonicelli L, Micucci C, Bilò MB, et al. IgE-mediated reactions to rifaximin and rifamycin SV and cross-reactivity among rifamycins. Allergy. 2009;64:1232–1233.
Tuberculous Osteomyelitis A Rare Form of Paradoxical Reaction
REFERENCES
To the Editors: aradoxical reaction is defined as a clinical or radiologic worsening of previous tuberculous lesions or development of new lesions after at least 1 month of antituberculous therapy (ATT), in a patient who initially responded to antituberculous therapy.1 PR has been recognized in 6–30% of patients being treated for tuberculosis (TB). These lesions are commonly central nervous system lesions, followed by new pleural diseases and then skin and lymph node lesions.2 Although uncommon, paradoxical reaction involving the spine and paraspinal tissue has been noted in a study conducted in Hong Kong.3 Here, we report a child with TB lymphadenitis who developed paradoxical reaction in the form of spinal and hip osteomyelitis. A 14-year-old girl presented in April 2011 with left cervical adenopathy for 1 and a half months for which a fine needle aspiration cytology was done that showed giant cells without necrosis. She underwent excision biopsy in April 2011 that was suggestive of tuberculous lymphadenitis. She was treated with ATT consisting of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol. She had been vaccinated with Calmette-Guérin bacillus at birth. Her cousin also had pulmonary TB 1 and a half years earlier and took ATT for 9 months. On examination, weight was 35.2 kg and height was
1. Al-Dabbagh M, Lapphra K, McGloin R, et al. Drug-resistant tuberculosis: pediatric guidelines. Pediatr Infect Dis J. 2011;30:501–505. 2. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep. 2000;49(RR-6):1–51.
The authors have no funding or conflicts of interest to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0787 DOI: 10.1097/INF.0000000000000323
Kyla J. Hildebrand, MD, FRCP(C), MSc CH
Department of Pediatrics Division of Allergy and Immunology University of British Columbia Vancouver
Adelle Atkinson, MD, FRCP(C)
Division of Allergy and Clinical Immunology Hospital for Sick Children Department of Paediatrics University of Toronto
Ian Kitai, MB, BCh, FRCP(C)
Division of Infectious Diseases Hospital for Sick Children and University of Toronto Toronto, Ontario, Canada
The Pediatric Infectious Disease Journal • Volume 33, Number 7, July 2014
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www.pidj.com | 787
Letters
147 cm. She had bilateral nontender cervical lymph nodes (2.5 cm × 2 cm). Other systems were normal. Her hemoglobin was 10.9 gm/dL, white blood cells count was 7500 cells/cumm (66% polymorphs, 34% lymphocytes) with erythrocyte sedimentation rate of 77 mm at end of 1 hour. She was continued on same treatment. In June 2011, she complained of pain in the left groin and buttock along with difficulty in walking and secondary amenorrhea. Her weight was 38.5 kg. The neurologic examination was normal. Radiograph of pelvis showed lysis of L5 vertebrae with narrowing of L5-S1, space and an osteomyelitic lesion of left pelvic bone. Magnetic resonance imaging of the spine showed focal osteomyelitis of the L5 vertebra and a lesion in the left iliac bone suggestive of TB osteomyelitis. Iliac bone curettage was done and sent for TB culture that did not
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The Pediatric Infectious Disease Journal • Volume 33, Number 7, July 2014
grow any mycobacteria. She was subsequently shifted to isoniazid (H), rifampicin (R) in September 2011 and ATT was discontinued in April 2012. She has remained asymptomatic on follow up. In nonsevere forms of paradoxic phenomena including recurrence of fever, enlargement of lymph nodes, increased pulmonary infiltrates or pleural effusion, when there is no severe clinical deterioration, no specific treatment other than continuing antituberculous drugs is required. However, steroids along with surgical intervention may be required in cases depending on the clinical deterioration such as enlargement of intracranial tuberculomas with obstructive hydrocephalus, massive pleural effusion compromising respiratory function.2 Our patient had developed a paradoxical reaction in the form of osteomyelitis, a rare occurrence, which showed remarkable
improvement without the help of immunomodulators.
Mary Joseph, DNB Ira Shah, MD, DPID
Pediatric TB Clinic B.J. Wadia Hospital for Children Mumbai, India REFERENCES
1. Carvalho AC, De Iaco G, Saleri N, et al. Paradoxical reaction during tuberculous treatment in HIV-seronegative patients. Clin Infect Dis. 2006;42:893–895. 2. Cheng VC, Ho PL, Lee RA, et al. Clinical spectrum of paradoxical deterioration during antituberculous therapy in non-HIV-infected patient. Eur J Clin Microbiol Infect Dis. 2002;21:803–809. 3. Cheng VC, Yam WC, Woo PC, et al. Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients. Eur J Clin Microbiol Infect Dis. 2003;22:597–602.
© 2014 Lippincott Williams & Wilkins
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The authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.pidj.com). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0787 DOI: 10.1097/INF.0000000000000295
temporary period in order for treatment to occur and lasts only for the duration of the treatment period. If the drug is discontinued and required in the future, the desensitization procedure must be repeated. The decision to pursue drug desensitization requires a high likelihood of drug allergy, a documented medical need for the drug, a lack of alternative agents and the benefits of drug desensitization outweigh the potential risks. Contraindications to desensitization include Steven-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, drug rash with eosinophilia and systemic symptoms, interstitial nephritis, hepatitis and hemolytic anemia.4 Our case highlights a rare case of rifampin hypersensitivity in a young child complicated by a lack of prophylaxis alternatives given the isoniazid-resistant strain of tuberculosis and crossreactivity among rifamycins.5 Rifampin desensitization protocols previously reported occurred mainly in adults involved premedication and were conducted in the intensive care unit. Premedication with antihistamine or corticosteroids was not used as these medications do not prevent IgE-mediated reactions and have the potential to mask early IgE symptoms at lower doses of the drug, thereby risking more serious reactions at higher doses. Drug desensitization should be performed under the guidance of an Allergy specialist, or at a minimum, a physician capable of treating anaphylaxis. The protocol outlined here may be a useful tool for other practitioners, particularly in areas where tuberculosis is endemic and treatment is essential.
3. Buergin S, Scherer K, Häusermann P, et al. Immediate hypersensitivity to rifampicin in 3 patients: diagnostic procedures and induction of clinical tolerance. Int Arch Allergy Immunol. 2006;140:20–26. 4. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259–273. 5. Antonicelli L, Micucci C, Bilò MB, et al. IgE-mediated reactions to rifaximin and rifamycin SV and cross-reactivity among rifamycins. Allergy. 2009;64:1232–1233.
Tuberculous Osteomyelitis A Rare Form of Paradoxical Reaction
REFERENCES
To the Editors: aradoxical reaction is defined as a clinical or radiologic worsening of previous tuberculous lesions or development of new lesions after at least 1 month of antituberculous therapy (ATT), in a patient who initially responded to antituberculous therapy.1 PR has been recognized in 6–30% of patients being treated for tuberculosis (TB). These lesions are commonly central nervous system lesions, followed by new pleural diseases and then skin and lymph node lesions.2 Although uncommon, paradoxical reaction involving the spine and paraspinal tissue has been noted in a study conducted in Hong Kong.3 Here, we report a child with TB lymphadenitis who developed paradoxical reaction in the form of spinal and hip osteomyelitis. A 14-year-old girl presented in April 2011 with left cervical adenopathy for 1 and a half months for which a fine needle aspiration cytology was done that showed giant cells without necrosis. She underwent excision biopsy in April 2011 that was suggestive of tuberculous lymphadenitis. She was treated with ATT consisting of isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol. She had been vaccinated with Calmette-Guérin bacillus at birth. Her cousin also had pulmonary TB 1 and a half years earlier and took ATT for 9 months. On examination, weight was 35.2 kg and height was
1. Al-Dabbagh M, Lapphra K, McGloin R, et al. Drug-resistant tuberculosis: pediatric guidelines. Pediatr Infect Dis J. 2011;30:501–505. 2. American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Recomm Rep. 2000;49(RR-6):1–51.
The authors have no funding or conflicts of interest to disclose. Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3307-0787 DOI: 10.1097/INF.0000000000000323
Kyla J. Hildebrand, MD, FRCP(C), MSc CH
Department of Pediatrics Division of Allergy and Immunology University of British Columbia Vancouver
Adelle Atkinson, MD, FRCP(C)
Division of Allergy and Clinical Immunology Hospital for Sick Children Department of Paediatrics University of Toronto
Ian Kitai, MB, BCh, FRCP(C)
Division of Infectious Diseases Hospital for Sick Children and University of Toronto Toronto, Ontario, Canada
The Pediatric Infectious Disease Journal • Volume 33, Number 7, July 2014
P
www.pidj.com | 787
Letters
147 cm. She had bilateral nontender cervical lymph nodes (2.5 cm × 2 cm). Other systems were normal. Her hemoglobin was 10.9 gm/dL, white blood cells count was 7500 cells/cumm (66% polymorphs, 34% lymphocytes) with erythrocyte sedimentation rate of 77 mm at end of 1 hour. She was continued on same treatment. In June 2011, she complained of pain in the left groin and buttock along with difficulty in walking and secondary amenorrhea. Her weight was 38.5 kg. The neurologic examination was normal. Radiograph of pelvis showed lysis of L5 vertebrae with narrowing of L5-S1, space and an osteomyelitic lesion of left pelvic bone. Magnetic resonance imaging of the spine showed focal osteomyelitis of the L5 vertebra and a lesion in the left iliac bone suggestive of TB osteomyelitis. Iliac bone curettage was done and sent for TB culture that did not
788 | www.pidj.com
The Pediatric Infectious Disease Journal • Volume 33, Number 7, July 2014
grow any mycobacteria. She was subsequently shifted to isoniazid (H), rifampicin (R) in September 2011 and ATT was discontinued in April 2012. She has remained asymptomatic on follow up. In nonsevere forms of paradoxic phenomena including recurrence of fever, enlargement of lymph nodes, increased pulmonary infiltrates or pleural effusion, when there is no severe clinical deterioration, no specific treatment other than continuing antituberculous drugs is required. However, steroids along with surgical intervention may be required in cases depending on the clinical deterioration such as enlargement of intracranial tuberculomas with obstructive hydrocephalus, massive pleural effusion compromising respiratory function.2 Our patient had developed a paradoxical reaction in the form of osteomyelitis, a rare occurrence, which showed remarkable
improvement without the help of immunomodulators.
Mary Joseph, DNB Ira Shah, MD, DPID
Pediatric TB Clinic B.J. Wadia Hospital for Children Mumbai, India REFERENCES
1. Carvalho AC, De Iaco G, Saleri N, et al. Paradoxical reaction during tuberculous treatment in HIV-seronegative patients. Clin Infect Dis. 2006;42:893–895. 2. Cheng VC, Ho PL, Lee RA, et al. Clinical spectrum of paradoxical deterioration during antituberculous therapy in non-HIV-infected patient. Eur J Clin Microbiol Infect Dis. 2002;21:803–809. 3. Cheng VC, Yam WC, Woo PC, et al. Risk factors for development of paradoxical response during antituberculosis therapy in HIV-negative patients. Eur J Clin Microbiol Infect Dis. 2003;22:597–602.
© 2014 Lippincott Williams & Wilkins
