Annular leukocytoclastic vasculitis associated with anti-tuberculosis medications: a case report.

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by  Chanprapaph, Kumutnart

Chanprapaphetal.JournalofMedicalCaseReports2013,7:34
JOURNAL OF MEDICAL
http://www.jmedicalcasereports.com/content/7/1/34
CASE REPORTS
CASE REPORT Open Access
Annular leukocytoclastic vasculitis associated with
anti-tuberculosis medications: a case report
Kumutnart Chanprapaph1*, Wanjarus Roongpisuthipong2 and Kunlawat Thadanipon1
Abstract
Introduction: Anti-tuberculosisdrug-induced cutaneous leukocytoclastic vasculitishas been rarely reported.To the
best ofour knowledge, this is the first reported case ofannular leukocytoclastic vasculitisassociated with
anti-tuberculosis drugadministration.
Case presentation: We report a case of annular leukocytoclastic vasculitis induced by anti-tuberculosis medication.
A 62-year-old Thai man presented to our facility with a generalized exanthematous rash on histrunk and
extremities thatresolved shortly afterwards. Subsequently,he developed multiple, erythematous-to-purplish,
non-blanchable macules and papules withan annular arrangementon his extremities. The skin rash occurred after
two weeks ofanti-tuberculosis medication. The histopathologyof thepurpuric skin lesion was consistent with
leukocytoclastic vasculitis. The skin lesion improved after discontinuation ofthe anti-tuberculosis drugs and
treatment withoral antihistamine and topical corticosteroid drugs. Streptomycin, ethambutol and ofloxacin were
administered as second-line anti-tuberculosis therapy during his hospitalization. Noadversereactions were
observed.
Conclusions: Leukocytoclastic vasculitisshould be considered in the differential diagnosis of annular
non-blanchable macules and papules. Although rare, anti-tuberculosis drugs should be consideredpotential causes
ofdrug-induced annular leukocytoclastic vasculitis.
Introduction Case presentation
Leukocytoclastic vasculitis (LCV) is a histologically A 62-year-old Thai man presented to our facility with a
defined condition characterized by necrotizing inflam- generalized erythematous maculopapular rash on his
mation around small dermal blood vessels, composed trunk and extremities. Our patient had been diagnosed
mainlyofneutrophilsandtheirdebris.Theusualpresen- as having pulmonary tuberculosis two weeks earlier. He
tation of LCV is polymorphous, with findings such as had long-standing hypertension and diabetes mellitus;
purpuric papules, urticaria and ulceration. An annular his treatment for this included daily amlodipine 5mg,
appearance of LCV is quite rare. Causes of LCV include metformin500mgandglipizide5mgdaily.Whentubercu-
drug reactions, malignancies, connective tissue diseases, losis was diagnosed, anti-tuberculosis therapy of isoniazid
infections and idiopathy [1,2]. An estimated 20 percent 300mg, rifampicin 450mg and ethambutol 800mg daily
to 30percent ofallvasculitis cases areattributed to drug was administered. After two weeks of anti-tuberculosis
reactions. LCV has rarely been reported in association medication,ageneralizedexanthematousrashappearedon
with anti-tuberculosis drugs [3]. We report an unusual his trunk and extremities (Figure 1). All anti-tuberculosis
clinical presentation of LCV following treatment with drugs were stopped after his admission due to a clinical
anti-tuberculosis drugs. suspicion of drug-induced adverse cutaneous reactions.
The exanthematous rash resolved within three days of
admission, leaving post-inflammatory hyperpigmentation.
One day later, multiple well-defined, non-blanchable,
erythematous-to-purplish macules and papules, some of
*Correspondence:[email protected]
1DivisionofDermatology,DepartmentofMedicine,FacultyofMedicine, which showed an annular arrangement, were noticed
RamathibodiHospital,MahidolUniversity,Bangkok,10400,Thailand
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Chanprapaphetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,
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Chanprapaphetal.JournalofMedicalCaseReports2013,7:34 Page2of4
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Figure2Multiple,well-defined,non-blanchable,erythematous
Figure1Generalizedexanthematousrashonthetrunkand
maculesandpapulesinanannulararrangement.
extremitiesofourpatient.
(Figure 2). He had no history of drug allergy and a review dermalbloodvessels,consistentwithcutaneoussmallves-
ofsystemswasunremarkable. selvasculitis(Figure4).Thesefindingswerediagnosticfor
Laboratory study findings were as follows: leukocytes, annular LCV associated with anti-tuberculosis drugs and
12.8×103 cells/mm3 (neutrophils 86 percent, lympho- drug-inducedcholestasis.Our patientwastreated withan
cytes 9 percent, monocytes 2 percent, eosinophils 2 per- oral antihistamine and topical corticosteroids. The skin
cent, basophils 1 percent); hemoglobin, 7.9g/dL; platelet eruptionclearedwithinoneweekwithouthyperpigmenta-
count, 215×103 cells/mm3; creatinine, 1.2mg/dL; aspar- tionandliverfunctiontestresultsreturnedtonormallim-
tate aminotransferase, 31U/L; alanine aminotransferase, its three weeks after the anti-tuberculosis drugs were
34U/L; alkaline phosphatase, 582U/L; γ-glutamyl trans-
ferase, 393U/L; totalbilirubin, 9.6mg/dL; directbilirubin,
8.4mg/dL; hepatitis B surface antigen, anti-hepatitis C
virusandanti-humanimmunodeficiencyvirus(HIV)test
results were all negative. Anti-nuclear antibody and anti-
neutrophil cytoplasmic antibody test results were also
negative. Urine analysis results showed no evidence of
proteinuria or hematuria. The findings from an abdom-
inal ultrasound were unremarkable. A skin biopsy from
a purpuric annular lesion on his leg showed peri-vascular
and interstitial infiltration of neutrophils with extravasa-
tionoferythrocytesandfibrindeposition(Figure3),char-
Figure3Histologyofapurpuricannularlesiononour
acteristic of LCV. A direct immunofluorescence (DIF)
patient’sleg.
study was positive for IgA, IgM and C3 along superficial
Chanprapaphetal.JournalofMedicalCaseReports2013,7:34 Page3of4
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that our patient should be classified as having annular
LCV.Thepresenceofextensivegeneralizederythematous
maculopapularrashonourpatient’strunkandextremities
might have obscured the initiation of the LCV lesions;
hence, onset of annular LCV was imprecise. The day
after resolution of the maculopapular rash, multiple,
well-defined, non-blanchable, erythematous-to-purplish
macules and papules,some of whichshowedanannular
arrangement, could be clearly noticeable.
AnnularLCVisanuncommonlyreportedclinicalvari-
ant of LCV. Annular LCV has been linked with systemic
diseasessuch assarcoidosis,ulcerative colitis,cryoglobu-
linemia associated with hepatitis B, Sjögren’s syndrome,
Figure4DirectimmunofluorescencerevealedpositiveIgA,IgM cervical cancer, lymphoma, and monoclonal and poly-
andC3resultsalongsuperficialdermalbloodvessels. clonal gammopathies [1,2]. Annular LCV has also been
linked to pregnancy, chlorzoxazone, sorafenib and amlo-
withdrawn. Streptomycin (750mg per day), ethambutol dipine besylate [7-10]. Amlodipine was not the culprit
(800mgperday)andofloxacin(400mgperday)weresub- drug for the development of LCV in our patient’s case
sequently administered as second-line anti-tuberculosis because he had been administered it for many years.
therapy during the hospitalization. No adverse reactions Moreover, his condition resolved despite continuation of
were observed. Therefore, he was subsequently treated amlodipine. An extensive review of the literature revealed
with ethambutol, ofloxacin and streptomycin without no previous case reports of annular LCV associated with
recurrenceoftheskinrash. anti-tuberculosisdrugs.
Discussion Conclusions
Cutaneous adverse reaction to anti-tuberculosis drugs In our patient’s case, the histology and resolution after
has been reported in up to 5 percent of patients treated. drug discontinuation suggest that anti-tuberculosis phar-
Common cutaneous reactions include pruritus, urticaria, maceuticals may have been the offending drugs that
maculopapular exanthems, fixed reaction and erythema caused annular LCV. LCV should be considered in the
nodosum.CutaneousLCVisarare complication ofanti- differential diagnosis of annular non-blanchable macules
tuberculosis medication [4]. The skin lesions typically and papules. Although rarely seen, anti-tuberculosis
improveuponwithdrawalofthemedication.Inaprevious drugs should be considered potential causes of drug-
study a case of rifampicin-induced and pyrazinamide- inducedannularLCV.
induced LCV was reported, and it was suggested that
antibodies to drugs contribute to the pathogenesis of Consent
vasculitis [5]. Cribier et al. first reported that some Written informed consent wasobtained from thepatient
patients with annular LCV constitute a distinctive sub- for publication of this manuscript and any accompany-
type, with the following criteria [6]: (1) multiple attacks ing images. Acopy of the written consent is available for
over years with sudden onset and spontaneous regression review bytheEditor-in-Chief ofthis journal.
after seven to 10 days, (2) annular purpuric patches that
Competinginterests
show centrifugal extension, (3) extension over the limbs
Theauthorsdeclarethattheyhavenocompetinginterests.
and trunk creating polycyclic lesions that clear leaving
mildhemosiderindeposition,(4)noextracutaneoussymp- Authors’contributions
WR,KTandKCpreparedthetextandcollectedallthemedicaldata.WRand
toms and good general health, (5) histological changes of
KCreviewedtheliterature,providedsuitablereferencesandassistedwiththe
LCVwithmildvascularchangesandintensepolymorpho- draftversionofthepaper.WRandKCreviewedandinterpretedthe
nuclear cell infiltration, and (6) complete clearance of all histopathologyfindingsandpreparedthemforthemanuscript.WR,KTand
KCreviewedthepaperandrevisedthefinalversion.Allauthorsreadand
lesions with dapsone (diamino-diphenyl sulfone). Our
approvedthefinalmanuscript.
patient’s case matches the second, third, fourth and fifth
criteria established by Cribier et al. Therefore, we cannot Acknowledgements
completely classify our patient’s case as a distinct subtype Wethankourpatient,whoallowedustopublishthiscase.
accordingtothecriteria;however,themorphologyofindi- Authordetails
vidual lesions is compatible with LCV arranged in an 1DivisionofDermatology,DepartmentofMedicine,FacultyofMedicine,
RamathibodiHospital,MahidolUniversity,Bangkok,10400,Thailand.2Division
annular pattern, and as a result of this together with the
ofDermatology,DepartmentofMedicine,FacultyofMedicine,Vajira
histologicandDIFfindingsdiagnosticforLCV,webelieve Hospital,UniversityofBangkokMetropolis,Bangkok,10300,Thailand.
Chanprapaphetal.JournalofMedicalCaseReports2013,7:34 Page4of4
http://www.jmedicalcasereports.com/content/7/1/34
Received:13July2012Accepted:14November2012
Published:31January2013
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doi:10.1186/1752-1947-7-34
Citethisarticleas:Chanprapaphetal.:Annularleukocytoclastic
vasculitisassociatedwithanti-tuberculosismedications:acasereport.
JournalofMedicalCaseReports20137:34.
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