leukocytoclastic vasculitis related to cocaine use

Actas Dermosifiliogr. 2011;102(10):825---836

CASE AND RESEARCH LETTERS

Leukocytoclastic Vasculitis Related toCocaine Use�

psychiatry department diagnosed the patient as having amixed personality disorder and treatment was initiated withamitriptyline, perphenazine, and diazepam. The general

Vasculitis leucocitoclástica asociada aconsumo de cocaína

To the Editor:

Vasculitis is a rare complication of cocaine abuse and posessignificant diagnostic and management problems. We reporta case of this type of vasculitis.

A 45-year-old woman with a history of cocaine abusefrom age 23 years consulted because of a 20-day history ofa widespread skin condition that affected practically thewhole body surface, was accompanied by fever and intensepain, and prevented her from walking. At the time of admis-sion, the patient was underweight, had facies dolorosa,normal vital signs, and dry mucosas. Physical examinationrevealed multiple ulcers of varying shape and size, with apurulent, foul-smelling exudate; several were covered bynecrotic slough (Fig. 1).

Additional tests, based on a suspected clinical diag-nosis of systemic vasculitis, gave the following results:white blood cell count, 12 500/�L; hemoglobin, 9.8 g/dL;reactive thrombocytosis, 658 000/�L; hypoalbuminemia,2.0 g/dL; alanine aminotransferase, 68 U/L; aspartateaminotransferase, 62 U/L; �-glutamyltransferase, 181 U/L;alkaline phosphatase, 326 U/L; creatinine clearance,88.3 mL/min with renal function of 86.6%; C-reactive pro-tein, 1.40 mg/dL; a negative Venereal Disease ResearchLaboratory test, negative rheumatoid factor; antineutrophilcytoplasmic antibodies (c-ANCA), 1:40; perinuclear (p)ANCA, 1:2560 U/mL; p-ANCA antilactoferrin, 48.2 U/mL;culture of the skin exudate, Escherichia coli; positive totalhepatitis A virus antibody; negative anti-hepatitis B andanti-hepatitis C virus antibodies; negative human immunod-eficiency virus (enzyme-linked immunosorbent assay). Skinbiopsy revealed leukocytoclastic vasculitis (Fig. 2).

The otorhinolaryngology department reported perfora-

� Please cite this article as: Salas-Espíndola Y, et al. Vas-culitis leucocitoclástica asociada a consumo de cocaína. ActasDermosifiliogr.2011;102:825-826.

Fe

1578-2190/$ – see front matter © 2010 Elsevier España, S.L. and AEDV. A

urgery department then performed surgical debridement ofhe ulcers and escharectomy. The patient was treated withntibiotics (trimethoprim-sulfamethoxazole, 160/800 mg,dministered intravenously every 12 hours for 14 days), anal-

igure 1 Photograph at presentation. Ulcers with a purulentxudate and covered with necrotic slough.

ll rights reserved.

826

Figure 2 Histopathology: mainly neutrophilic, abundantperivascular inflammatory infiltrate that infiltrates and partiallydtm

apscstc

ltp

tcdvv

BSeirgtdct

texMsopaads

wvoUfsetadc(bast

3,7

estroys blood vessel walls; prominent leukocytoclasis and mul-iple foci of vascular thrombosis (periodic acid-Schiff, originalagnification x40).

fter 37 days, with the presence of granulation tissue andartial reepithelialization of the ulcerated areas. Diagno-is at discharge was cocaine-related vasculitis based on thelinical findings, histopathological study, the positivity oferum markers (p-ANCA and lactoferrin), a history of long-erm consumption of the drug, and the exclusion of otherauses.

Follow-up confirmed the reepithelialization of mostesions, which developed into hypertrophic scars and retrac-ile keloids, currently awaiting surgical treatment by thelastic surgery department (Fig. 3).

Cocaine consumption is increasing worldwide, leadingo a rise in related diseases. The spectrum of skin lesions

s

tw

Figure 3 Photograph at 7 months of follow-up. There

CASE AND RESEARCH LETTERS

uerger disease, pyoderma gangrenosum, and gangrene.1,2

ome authors hold levamisole, an adulterant found in thend product, responsible for the damage in cases involv-ng microvascular thrombosis and neutropenia.3 There areeports of cocaine consumption in patients with Wegenerranulomatosis,4 and since both may cause midline destruc-ive lesions of the face, distinguishing between them can beifficult. In our patient, the absence of granulomatous vas-ulitis of the respiratory tract, renal involvement, and highiters of c-ANCA enabled us to rule out this possibility.

The study protocol for cocaine-related vasculitis is iden-ical to drug-related vasculitis and includes a blood count,rythrocyte sedimentation rate, routine biochemistry, chest-ray, urinalysis, liver function tests, and fecal occult blood.ore specific studies should subsequently be considered,

uch as histopathology with or without direct immunoflu-rescence, anticardiolipin antibodies, homocysteine levels,roteins S and C, and cryoglobulins. Serum levels of ANCA,ntinuclear antibodies, rheumatoid factor, complement,nd hepatitis B and C virus antibodies should also beetermined, together with human immunodeficiency viruserology.5

The case presented here was a drug-dependent patienthose clinical lesions were compatible with necrotizingasculitis confirmed by histopathology, with a diagnosisf an ANCA-positive cutaneous vasculitis (p-ANCA, 1:2560/mL, antilactoferrin antibodies, 48.2 U/mL). The dif-erential diagnosis included other forms of ANCA-positivemall-vessel vasculitis. The role of ANCA in the pathogen-sis of vasculitis is still unclear. One hypothesis suggestshat ANCA stimulate neutrophil degranulation, activation,nd apoptosis, leading to direct and indirect endothelialamage.6 Drug-induced ANCA show a perinuclear fluores-ence pattern (p-ANCA) and positivity to several antigensmyeloperoxidase, cathepsin G, proteinase 3, azurocidin,actericidal/permeability-increasing protein, lactoferrin,nd human neutrophil elastase). Reports in the literatureuggest that the presence of lactoferrin and human neu-rophil elastase supports the diagnosis of a cocaine-related

The management of these patients is still a mat-er of debate, but good outcomes have been reportedith the use of systemic steroids, nonsteroidal immuno-

is reepithelialization of the lesions and scarring.

1

2

3

4

5

CASE AND RESEARCH LETTERS 827

suppressants, antihistamines, dapsone, pentoxifylline, andintravenous immunoglobulin.8 Our patient stopped takingcocaine and was treated with thalidomide and systemicsteroids. Although the outcome was excellent, significantscarring could not be avoided.

References

. Stone JH. Vasculitis: a collection of pearls and myths. Rheum DisClin North Am. 2007;33:691---739.

. Roche E, Martínez-Menchón T, Sánchez-Carazo JL, Oliver V,Alegre de Miquel V. Piodermas gangrenosos eruptivos asociados alconsumo de cocaína inhalada. Presentación de dos casos. ActasDermosifiliogr. 2008;99:727---30.

. Walsh NMG, Green PJ, Burlingame RW, Pasternak S, Hanly JG.Cocaine related retiform purpura: evidence to incriminate theadulterant, levamisole. J Cutan Pathol. 2010;37:1212---9.

. Neynaber S, Mistry-Burchardi N, Rust C, Samtleben W,Burgdorf WHC, Seitz MA, et al. PR3-ANCA-positive necrotiz-ing multi-organ vasculitis following cocaine abuse. Acta DermVenereol. 2008;88:594---6.

. Merkel PA. Drug-induced vasculitis. Rheum Dis Clin North Am.2001;27:849---62.

6. Khasnis A, Langford CA. Update on vasculitis. J Allergy ClinImmunol. 2009;123:1226---36.

7. Csernok E, Lamprecht P, Gross WL. Clinical and immunologi-cal features of drug-induced and infection-induced proteinase3-antineutrophil cytoplasmic antibodies and myeloperoxidase-antineutrophil cytoplasmic antibodies and vasculitis. Curr OpinRheumatol. 2010;22:43---8.

8. Pham T, Heinly C, Herman C, Selim MA. P-ANCA positive cocaineassociated vasculitis: a case report. J Cutan Pathol. 2008;32:109.

Y. Salas-Espíndola,a A. Peniche-Castellanos,a,∗

I. López-Gehrke,a P. Mercadillo-Pérezb

a Servicio de Dermatología, Hospital General de México,México, D.Fb Servicio de Dermatopatología, Hospital General deMéxico, México, D.F

∗ Corresponding author.E-mail address: amelia peniche@yahoo.com.mx(A. Peniche-Castellanos).

Alopecia Areata After Biologic Therapy:Report of a Case Related to Adalimumab�

Alopecia areata y terapias biológicas.Presentación de un caso asociado aadalimumab

To the Editor:

Alopecia areata (AA) is an autoimmune disorder causing non-scarring hair loss. It is an organ-specific response at thecellular level and is mediated by CD4+ and CD8+ T cells.These lymphocytes may be activated by autoantigens atthe hair root, inducing inflammation that eventually leadsto hair loss. The increased use of biologic therapies hasrecently led to a growing number of publications discussingthe possible link between these treatments and autoimmunedisorders, including AA.

A 39-year-old man with plaque psoriasis on a regimen ofadalimumab (40 mg) twice weekly presented with 2 alope-cia plaques after 1 year of treatment. The plaques, locatedon the cranial vertex, had appeared over the previous fewweeks (Fig. 1). The patient had no family or personal historyof AA and reported no events involving infection, vaccina-tion, or stress prior to the loss of hair. AA was diagnosed,adalimumab treatment was stopped, and a daily applica-tion of clobetasol propionate 0.05% cream was prescribed.After 6 months the diameter of both alopecia plaques had

� (TNF-�) and has been approved for the treatment ofrheumatoid arthritis, ankylosing spondylitis, Crohn disease,psoriasis, and psoriatic arthritis. TNF-� is a proinflamma-tory cytokine in the body’s immune system, but when itis neutralized by anti-TNF-� antibodies like adalimumab,autoimmune disorders such as systematic sclerosis and sys-temic lupus erythematosus have been known to develop.1

The role of TNF-� in the physiopathology of these processesis complex, but the cytokine has been shown to originatein the mononuclear cells that surround the hair follicle inAA1 and inhibit hair follicle growth during in vitro testing.2

TNF-� is thus linked to hair loss. Accordingly, anti-TNF-�medications and other biologic therapies have been usedto treat AA, but with poor results; in some sporadic casessatisfactory responses have been reported, but no largestudy has demonstrated any significant therapeutic effectsof etanercept,3 alefacept,4 or efalizumab.5

not changed despite the withdrawal of adalimumab.Adalimumab is a recombinant and fully humanized mon-

oclonal antibody that works against tumor necrosis factor

� Please cite this article as: Neila J, et al. Alopecia areata y te-rapias biológicas. Presentación de un caso asociado a adalimumab.Actas Dermosifiliograf.2011;102:827-828.

Fa

igure 1 Alopecia areata plaque located on the cranial vertexfter a year of adalimumab treatment.