A review was made of the 36 paediatric patients in whom the diagnosis of erythema nodosum had been established between 1977 and 1996 at the Department of Paediatrics, University of Bern, Switzerland. Infectious diseases were associated with erythema nodosum in 20 (including 10 streptococcal infections) and non-infectious inflammatory diseases in 8 patients. None of the 36 patients had tuberculosis or had been exposed to sulphonamides, phenytoin or hormonal contraceptives. There were eight patients in whom either the associated disease was not diagnosed, or there was no other disease. Conclusion Most cases of erythema nodosum are nowadays caused by non-mycobacterial infectious diseases or by non-infectious inflammatory disease

Bianchetti, M.

Hassink, R.

Jacomella, V.

Laux-End, R.

Pasquinelli-Egli, C.

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IMMUNOLOGY / ALLERGOLOGYR. I. Hassink á C.E. Pasquinelli-Egli á V. JacomellaR. Laux-End á M.G. BianchettiConditions currently associated with erythema nodosumin Swiss childrenReceived: 29 April 1997 /Accepted: 26 May 1997Abstract A review was made of the 36 paediatric pa-tients in whom the diagnosis of erythema nodosum hadbeen established between 1977 and 1996 at the Depart-ment of Paediatrics, University of Bern, Switzerland.Infectious diseases were associated with erythemanodosum in 20 (including 10 streptococcal infections)and non-infectious inflammatory diseases in 8 patients.None of the 36 patients had tuberculosis or had beenexposed to sulphonamides, phenytoin or hormonalcontraceptives. There were eight patients in whom eitherthe associated disease was not diagnosed, or there wasno other disease.Conclusion Most cases of erythema nodosum arenowadays caused by non-mycobacterial infectiousdiseases or by non-infectious inflammatory diseases.Key words Child á Erythema nodosum á Inflammatorybowel disease á Streptococcal infections á TuberculosisIntroductionIn childhood erythema nodosum is the most prevalentpanniculitis. It has a characteristic clinical picture andthe diagnosis can be made on the basis of physical ex-amination alone [5, 6]. Erythema nodosum has been as-sociated with various infectious and non-infectiousdisorders [5, 6]. In addition, various pharmacologicalagents have also been considered responsible for thispanniculitis [5, 6]. The relative weight of the variouscauses of erythema nodosum is influenced by geograph-ical and racial factors as well by the age of the patients[1–6, 8–10, 12]. Their importance may also vary fromtime to time [1–6, 8–10, 12]. Previous surveys emphasizedmycobacterial and streptocooccal infections as the con-ditions most often linked with erythema nodosum, but abetter control of these diseases is now possible. Therehave been no general series of cases reported in recentyears which might mirror these mutations. The purposeof this study was to review the conditions associated witherythema nodosum in the period 1977 to 1996 as en-countered in a paediatric referral hospital in Switzerland.Patients and methodsA review was made of all patients aged 16 years or less in whom thediagnosis of erythema nodosum had been established between 1977and 1996 at the Department of Paediatrics, University of Bern,Switzerland. For this purpose, the clinical and the laboratory recordsof the Department of Paediatrics and those of the referring familydoctors were evaluated in terms of established criteria for the diag-nosis of associated conditions. The use of sulphonamides, phenytoinand hormonal contraceptives was expressly inquired. Total whiteblood cell count, erythrocyte sedimentation rate, tuberculin skin testand chest roentgenography had been performed in all children. Ad-ditional investigations were performed in patients with a positivetuberculin test. Information on follow up was obtained directly bythe patient or by the referring physicians 6 months or more after theskin lesion had resolved. The results are expressed as median andinterquartile range. The v2-test and theKruskal-Wallis testwere usedto analyse the results obtained in the various subgroups of patients.P < 0:05 was accepted to indicate statistical significance.ResultsAll 36 patients (18 girls and 18 boys, aged between 1.5and 16 years, median 10 years) were Caucasian. The skinlesions were confined to the shins and knees in 29 cases.In 7 patients the rash was concurrently found on theforearms (n  7) or the face (n  1). Infectious diseaseswere diagnosed in 20 patients and non-infectious dis-eases in 8 (Table 1). None of the patients had tubercu-losis. There were 8 patients in whom either theassociated disease was not diagnosed, or there was noother disease. General information on the three dierentEur J Pediatr (1997) 156: 851–853 Ó Springer-Verlag 1997R. I. Hassink á C.E. Pasquinelli-Egli á V. JacomellaR. Laux-End á M.G. Bianchetti (&)Kinderklinik, Inselspital, CH-3010 Bern, Switzerland,Tel.: +31 6329479, Fax: +31 6329444,E-mail: mbianche@insel.chgroups of patients appears in Table 2. The patientswithout associated diagnosis tended to be younger byapproximately 5 years than those with associated infec-tious or non-infectious disease. Duration of the rash waslonger by approximately 10 days in patients with anunderlying non-infectious disease. In three patients witha non-infectious underlying disease the final diagnosis(each one patient with Crohn disease, Behc¸et disease orsarcoidosis) was made 2, 3 and 4 months after resolutionof the skin lesions. None of the 36 patients had beenexposed to sulphonamides, phenytoin or hormonalcontraceptives.Erythema nodosum tended to recur in the patientwith sarcoidosis, in one patient with Crohn disease andin one patient with erythema nodosum associated withupper respiratory infection.DiscussionThe present report indicates that most cases of child-hood erythema nodosum are nowadays caused either bynon-mycobacterial infectious diseases or by non-infec-tious inflammatory diseases. The most common infec-tious precipitating agents are streptococcal infections,non-streptococcal respiratory infections likely caused byunidentified viral agents and other viral or bacterial in-fections. The most common non-infectious causes areinflammatory bowel diseases, sarcoidosis, Behc¸et diseaseor collagen vascular diseases [5–7]. The tendency forerythema nodosum to occasionally antedate othermanifestations of non-infectious systemic diseases notedin this survey corroborates the data of the literature [7].In spite of information on follow up for at least 6months there was a large minority of patients in whomthe associated disease was not diagnosed, or there wasno other disease [1–6, 8–10, 12].Sulphonamides, phenytoin and hormonal contra-ceptives have also been considered responsible for ery-thema nodosum in adulthood [5, 6] but none of ourpaediatric patients had been exposed to these agents.In the past, tuberculosis was the foremost cause oferythema nodosum but in this survey tuberculosis failedto account for erythema nodosum [1–6, 8–10, 12]. Afterdecades of decline in the incidence, the number of tu-berculosis cases has tended to increase over the last yearsin Switzerland as a consequence of the immigration fromhigh prevalence countries and the outbreak of humanimmunodeficiency virus [11, 13]. It is therefore assumedthat tuberculosis still deserves consideration in childrenwith erythema nodosum [5, 6].Table 1 Disorders associated with erythema nodosum in 28 out ofthe 36 patients. In the remaining 8 patients the associated diseasewas not diagnosed, or there was no other diseaseCondition CasesStreptococcal infections– pharyngitisa 8– impetigob 1– cellulitisb 1Non-streptococcal respiratory infections– upper respiratory tract 2– lower respiratory tract 2Burkholderia cepacia pulmonary infectionc 1Parvovirus B19 1Infectious mononucleosis 1Infectious gastro-enteritisd 3Ulcerative colitis 3Crohn disease 3Sarcoidosis 1Behc¸et disease 1a b-haemolytic streptococcus cultured n  4, strongly increasedantistreptolysin titre n  2 or both n  2b b-haemolytic streptococcus culturedc Patient with cystic fibrosisd Yersinia enterocolitica and Salmonella enteritidis each on oneoccasionTable 2 Conditions associated with erythema nodosum in 36 paediatric patients. Results are given as median [interquartile range betweenbrackets]InfectiousdiseasesNon-infectiousdiseasesNo associateddiagnosisAllCases 20 8 8 36Female:male 10:10 5:3 3:5 18:18Age, years 10 [18.8–13] 11 [10–14] 4.8a [3.4–8.4] 9.6 [5.3–13]Clinical findingsFeverb 13 4 3 20Arthralgia without synovitis 6 2 2 10Synovitis 3 2 0 5Rash duration, days 12 [11–15] 21a [16–30] 10 [9–11] 12 [10–16]Laboratory findingsElevated white cell countc (n) 9 5 2 16Left shiftd (n) 4 3 0 7Elevated sedimentation ratee (n) 15 8 3 26a Versus the remaining groupsb >38.0°Cc Leucocytes >15 ´ 109/ld Nonsegmented polymorphonuclear leucocytes >15%e >30 mm/h852It is concluded that in Switzerland most cases ofchildhood erythema nodosum are nowadays caused ei-ther by non-mycobacterial infectious diseases or by non-infectious inflammatory diseases.References1. Blomgren SE (1972) Conditions associated with erythemanodosum. N Y State J Med 72:2302–23042. Chiappo GF, Balbo L, Picco V, Licata D, Mignone F, Bo C(1977) L’eritema nodoso nell’infanzia. Inquadramento diag-nostico e contributo casistico. Arch Sci Med (Torino) 134:253–2743. El Zawahry M (1971) Erythema nodosum: a study of 60 cases.Int J Dermatol 10:145–1504. Fernandes NC, Maceira J, Muniz M (1994) Erythema nodo-sum: prospective study of 32 cases. Rev Inst Med Trop SaoPaulo 36:507–5135. Fox MD, Schwartz RA (1992) Erythema nodosum. Am FamPhysician 46: 818–8226. Hannuksela M (1986) Erythema nodosum. Clin Dermatol4:88–957. Hyams JS (1994) Extraintestinal manifestations of inflamma-tory bowel disease in children. J Pediatr Gastroenterol Nutr19:7–218. Kibel MA (1970) Erythema nodosum in children. S Afr Med J44:873–8769. Laurence B, Stone DGH, Philpott MG, Wright T, Page APM,Harvey CC, Colver T, Gordon RR, Illingworth RS, Lorber J(1961) Aetiology of erythema nodosum in children: a study of agroup of paediatricians. Lancet 278:14–1610. Romero Gonzalez J, Fernandez Ortiz B (1988) Eritema nodosoen la infancia. An Esp Pediatr 29:317–31911. Shang H, Desgrandchamps D (1995) Tuberkulose in derSchweiz. Praxis 84:1114–111712. Simila¨ S, Pietila¨ J (1965) The changing etiology of erythemanodosum in children. Acta Tuberc Scand 46:159–16813. Starke JR, Jacobs RF, Jereb J (1992) Resurgence of tubercu-losis in children. J Pediatr 120:839–855853

Conditions currently associated with erythema nodosum in Swiss children

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Conditions currently associated with erythema nodosum in Swiss children

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