Background:

Fluoroquinolones are being increasingly used in pediatric practice in India. Concerns about the potential chondropathic effects observed in juvenile animals have not been substantiated in Humans. Increasingly tendinopathy has been recognized as a class effect of fluoroquinolones in recent years especially in the older population. Experimental studies have demonstrated an apoptotic influence of ofloxacin on tenocytes. In view of its excellent antimicrobial spectrum especially in enteric fever and efficacy of oral dosing, prescriptions of ofloxacin in general pediatric practice have been steadily rising. Of all the fluoroquinolones, ofloxacin has been reported to have the highest relative risk of 10.1 for Achilles tendonitis. Very little literature exists on the occurrence of fluoroquinolone associated joint and tendon disorders in India children.

Objective:To study the pattern of arthropathy and soft tissue rheumatism in children exhibited to ofloxacin for enteric fever in a hospital setting.

Setting: Paediatric unit of 2 Armed Forces hospitals in Uttar Pradesh, India.

Materials and Methods:

Children below 12 years age reporting to the Pediatric OPD with arthralgia, arthritis or tenosynovitis, within 30 days of being exhibited to ofloxacin either in OPD or during hospitalization for a diagnosis of enteric fever were studied from April 2003 to September 2005. Basis of diagnosis of enteric fever was either culture positivity or 4 fold rise/fall in Widal titers in the clinical setting. An ofloxacin induced/associated event was defined after exclusion of other causes which could explain the symptoms.

Results:

During the study period, of the 61 children treated with ofloxacin for a diagnosis of enteric fever, 47 children could be followed up till at least 1 month after cessation of course of ofloxacin. Culture positivity for salmonella typhi was seen in 18 while the rest had positive Widal titers (4 fold titers). Thirty nine children inclusive of all the culture positive cases had been hospitalized (mean stay 10 days (range: 6 to 35 days) while the rest had received treatment on outpatient basis. There was no mortality. Four out of the 47 (8.5%) children had features suggestive of joint or tendon disorder during (50%) / within 30 days (50%) following ofloxacin exposure. The clinical features of the affected children are given in Table 1. Arthralgias and ankle enthesitis was common. None of the children had arthritis and none of the episodes had any significant systemic features except in one case wherein ofloxacin had to be stopped and child switched over to ceftriaxone. Except for raised ESR, rest of investigations was negative. All the children were managed with rest, physiotherapy and ibuprofen for the pain. No tendon ruptures were noted in our study population.

Conclusion:

The temporal association of symptoms and the specific pattern of transient and self limiting involvement of periarticular tissues and tendinous insertions suggest an enthesitic process related to ofloxacin. Definite exclusion of a post-salmonella infection reactive rheumatism, however, remains difficult. In view of the increasing use of ofloxacin in pediatric population in India, more number of studies are required to define the soft tissue rheumatism and tendinopathies with this group of drugs.

	Case 1	Case 2	Case 3	Case 4
Age/sex/ Diagnosis	11 yr/male/culture positive enteric fever	6 yr/male/culture positive enteric fever	5 yr/female/Widal positive	9 yr/female/ Widal positive
Clinical presentation	Fever with Hepatosplenomegaly of 9 days duration	Fever, abdominal pain, hepatomegaly	Fever of 12 days unresponsive to empirical antimalarials with hepatomegaly and mild diarrhea of 7 days duration.	Fever vomiting, hepatomegaly.
Time to afebrile period	Afebrile day 5	Afebrile day 12	Afebrile day 5	Afebrile day 4
Duration of ofloxacin	Ofloxacin 7 days	Ofloxacin 10 days	Ofloxacin 7 days	Ofloxacin 7 days
Rheumatic features	Developed bilateral Achilles tendonitis and ankle enthesitis on day 3 of ofloxacin	Developed bilateral wrist and knee pains and flexor synovitis with generalized rash on day 10 of ofloxacin	Developed asymmetrical polyarthralgia followed by bilateral ankle swellings and Achilles tendonitis 10 days after stopping ofloxacin	Bilateral patellar and ankle tendonitis 22 days after cessation of ofloxacin
Investigations	ESR 34 mm 1 st hr, TLC 9,300/mm3, P 45%, CRP, ANA, RA Factor –ve	ESR 47 mm 1 st hr, TLC 15,400/mm3, P 78%, CRP, ANA, RA Factor –ve	ESR 22 mm 1 st hr, TLC 10,200/mm3, P 55%, CRP, ANA, RA Factor –ve	ESR 19 mm 1 st hr, (WG), TLC 6700/mm3, P 67%, CRP, ANA, RA Factor –ve
Course	Persistent ankle thickening for 3 weeks; soft tissue thickening on X-rays	Rash and arthralgia disappeared after Ofloxacin stopped; switched to ceftriaxone; flexor synovitis disappeared after 10 days	Recovered after 10 days	Recovered after 5 days

RCIAPCON 2005 - Conference Abstracts.Pediatric Oncall [serial online] 2006 [cited 15 June 2006(Supplement 6)];3. Available from:
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ofloxacin_associated_rheumatism.asp