ARTHRITIS & RHEUMATISM
Vol. 43, No. 3, March 2000, pp 584–592
© 2000, American College of Rheumatology
ERYTHEMA NODOSUM
Etiologic and Predictive Factors in a Defined Population
CARLOS GARCI
´
A-PORRU
´
A, MIGUEL A. GONZA
´
LEZ-GAY, MANUEL VA
´
ZQUEZ-CARUNCHO,
LUIS LO
´
PEZ-LAZARO, MERCEDES LUEIRO, MARIA L. FERNA
´
NDEZ,
JAVIER ALVAREZ-FERREIRA, and RAMO
´
N M. PUJOL
Objective. To examine the frequency and features
of erythema nodosum (EN), establish disease associa-
tions, and identify the optimal set of predictors for the
occurrence of secondary EN.
Methods. We performed a retrospective study of
an unselected population of patients 14 years and older
with biopsy-proven EN diagnosed at a referral hospital
between 1988 and 1997. Patients were classified as
having either idiopathic EN or EN secondary to other
diseases if the skin nodules occurred in the context of a
well-defined disease, or if there was a precipitating event
in close temporal proximity to the onset of EN.
Results. One hundred six patients (82 women)
were diagnosed as having biopsy-proven EN. At the time
of diagnosis, no precipitating events or underlying dis-
eases were identified in 36.8% of patients. Sarcoidosis
and nonstreptococcal upper respiratory tract infections
(URI) were the most common conditions associated with
secondary EN. Only 1 of 35 patients with an initial
diagnosis of idiopathic EN and a followup of at least 1
year was finally diagnosed as having secondary EN. The
best predictive model of secondary EN included an
abnormal results on a chest radiograph, a previous
history of nonstreptococcal URI, and a significant
change in antistreptolysin O (ASO) titer in 2 consecu-
tive determinations performed in a 2–4-week interval.
Also, the presence of peripheral synovitis, a positive
tuberculin skin test, and a history of diarrhea suggested
the presence of secondary EN. This model showed high
sensitivity and specificity.
Conclusion. Idiopathic EN is common. A basic
procedure including careful medical history-taking, a
physical examination for peripheral synovitis, 2 consec-
utive ASO determinations, a tuberculin skin test, and
chest radiography may be sufficient to diagnose EN.
Erythema nodosum (EN) is the most common
cause of inflammatory nodules and usually affects the
lower extremities. It is a self-limiting disease character-
ized by lesions that evolve from inflammatory, painful
and tender, nonulcerating, nonscarring, cutaneous and
subcutaneous red nodules, which are typically multiple
and bilateral, becoming bruised in appearance, and,
finally, resolving completely. EN may be associated with
a wide spectrum of systemic diseases, infections, or
various drugs. The prognosis with regard to the skin
lesions is usually excellent, but the presence of a possible
underlying condition needs to be excluded (1–5).
The purpose of this study was to examine the
frequency, features, and outcome of EN, establish dis-
ease associations, and identify the optimal set of predic-
tors for the diagnosis of either idiopathic or secondary
EN. We reviewed the clinical symptoms, laboratory
findings, and followup of all patients 14 years and older
with biopsy-proven EN diagnosed between 1988 and
1997 in a defined area of northwestern Spain.
PATIENTS AND METHODS
We studied retrospectively the case records of all
patients diagnosed with biopsy-proven EN in the department
of medicine of Hospital Xeral-Calde from January 1988
through December 1997. Since the pediatric population was
not studied in our department, we examined the spectrum of
Carlos Garcı ´a-Porru ´a, MD, PhD, Miguel A. Gonza ´lez-Gay,
MD, PhD, Manuel Va ´zquez-Caruncho, MD, Luis Lo ´pez-Lazaro, MD,
PhD, Mercedes Lueiro, MD, Maria L. Ferna ´ndez, MD, Javier Alvarez-
Ferreira, MD: Hospital Xeral-Calde, Lugo, Spain; Ramo ´n M. Pujol,
MD, PhD: Hospital Santa Creu i San Pau, Barcelona, Spain.
Address reprint requests to Miguel A. Gonza ´lez-Gay, MD,
PhD, Rheumatology Division, Hospital Xeral-Calde, c) Dr. Ochoa s/n,
27004 Lugo, Spain.
Submitted for publication June 7, 1999; accepted in revised
form November 19, 1999.
584