Cassano, N.

Coviello, C.

Francesco LOCONSOLE

Vena, G. A.

English

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INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY Vol. 19, no. 1,237-240 (2006)CASE REPORTINFLIXIMAB IN RECALCITRANT SEVERE ATOPIC ECZEMA ASSOCIATED WITHCONTACT ALLERGYN. CASSANO, F. LOCONSOLE, C. COVIELLO and G.A. VENADepartment ofInternal Medicine, Immunology and Infectious Diseases, II Unit ofDermatology,University ofBari, ItalyReceived February 14, 2005 - Accepted September 22, 2005Inffiximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal antibody which iseffective in diseases associated with aT-helper (Th) 1 response, such as rheumatoid arthritis, Crohn'sdisease and psoriasis. There are sporadic case reports of atopic dermatitis (AD) induced or precipitated byanti-TNF-alpha therapy, which have been attributed to the switch towards Th2-mediated reactions. Wereport the case of a 30-year-old man with long-standing severe AD associated with contact allergy andpoorly responding to conventional treatments. The use ofinffiximab resulted in a dramatic amelioration ofAD lesions and pruritus, persisting at follow-up examinations over a 3-year period. Probably, theunexpected response to infliximab therapy in this case might be due to some peculiar features of AD in ourpatient (i,e. chronic-continuous course and concomitant contact allergy) which could have been responsiblefor a more preponderant recruitment ofThl cells as compared to "common" forms of AD.Infliximab is an anti-tumour necrosis factor (TNF)-alpha chimeric monoclonal antibody which iseffective in diseases associated with aT-helper (Th) Iresponse, such as rheumatoid arthritis, Crohn's diseaseand psoriasis (1-5). There are sporadic case reports ofimmune-mediated cutaneous eruptions induced orprecipitated by anti-TNF-alpha therapy, includingatopic dermatitis (AD) (6-8). Unaware of the possiblerisk of aggravating AD with anti- TNF- alpha therapy,in January 2003, we used infliximab in a case ofsevererecalcitrant AD associated with contact allergy.MATERIALS AND METHODSA 30-year-old man presentedwitha 22-yearhistoryofAD,which had notably worsened in the last 4 years, beingcharacterized by a continuouscourse, long-lasting widespreadlesionsand incoercible pruritus, refractory to topical steroidsand HI-receptorantagonists. The patientalsoexperiencedtwoepisodes of erythrodermia associated with generalizedlymphadenopathy. The deterioration of AD includedpronounced impact on quality of life and mood disorders sothat after two years the patient received treatment withparoxetine and benzodiazepines. He also presented aconcomitant contact sensitisation to nickel sulphate andpotassium bichromate but prevention did not cause anysubstantial benefiton skin manifestations and symptoms. Ontwo separate occasions over the last three years,histopathological analysisof skin samplestaken from lesionalskin showedthe typical findings of an eczematousdermatitis.Systemic corticosteroids and cyclosporin gave onlypartial temporary relief of AD and had to be discontinuedafter a few months because of side effects, whereasleukotrieneantagonists and high-dose immunoglobulinsdidnot show any effects. Treatment with 0.1% tacrolimusKey words: atopic dermatitis, contact allergy, infliximab, TNF-alpha, T helper cellsMailing address:Prof. G.A. Vena, MDMIDlM Department. 2nd Unit of Dermatology - University ofBariPoliclinico, Piazza Giulio Cesare, 1170124 Bari, ItalyTcI.lFax: 0039 080 5478920E-mail: g.vena@dermatologia.uniba.it2370394-6320 (2006)Copyright cD by BIOLIFE.s.a.s.This publicationand/or article is for individualuse only and may not be funherreproducedwithout written pennission from the copyright holder.Unauthorized reproduction may results in financial and other penalties238 N. CASSANO ET AL.ointment caused a sustained improvement of facial lesions,but an unsatisfactory control of pruritus and only aslight/moderate patient's self-perceived effect on AD locatedon other sites because body lesions were diffuse andcontinuously relapsing. For this reason, the patientdiscontinued tacrolimus ointment after 6 months. Then,immediately prior to the admission to our unit, the patientwas treated with topical mometasone furoate and cetirizine.Relevant medical history also included childhood asthmaand rhinitis, and persistent hyperimmunoglobulinemia E(>5,000 kU VI). Hyper-Igf syndrome was excluded on thebasis of the absence ofother typical manifestations (facial orskeletal abnormalities, and relapsing infections) (9).Diagnosis of AD was confirmed according to Hanifin andRajka criteria (10). On clinical examination, AD wascharacterized by diffuse confluent lesions on the trunk andlimbs. SCORAD index (11), used to assess the extent andintensity ofAD lesions and the severity of symptoms, had avalue of 74. Histological examination of a biopsy specimendisclosed the features of AD in chronic phase, with sparsemicrovesicular spongiotic aspects and prominentpsoriasiform changes. After obtaining a written informedconsent, the patient was treated with infliximab.RESULTSInfliximab 3 mg/kg was given intravenously, and,within a few hours, the patient noted a marked relief ofpruritus. During the post-infusion period, thesymptomatic therapy already used by the patient wascontinued as needed. After a week, AD showed a slightimprovement (SCORAD: 58) which becameprogressively more evident (SCORAD at 4 weeks:21.3). At 6 weeks, because of pruritus exacerbation, asecond infusion of infliximab was administered at thedose of 5 mg/kg and a rapid antipruriginous effect wasagain obtained. AD notably improved in the subsequent4 weeks, with a SCORAD value of 13.6. Treatment withmometasone and cetirizine was gradually tapered andcompletely stopped within 3 months, as waspsychotherapy. Since then, regular follow-upevaluations have shown a stable improvement of ADand itch (maximum value of SCORAD 25), withsymptom-free periods during summer months andsuccessful control offlares with tacrolimus ointment. Anindirect measure ofAD improvement is also provided bythe consumption of tacrolimus tubes, the number ofwhich had an approximately 3- to 4-fold reduction ascompared with the number previously used. Moreover,in the follow-up evaluations, topical tacrolimus wasapplied on sparse and limited areas, especially on trunk,face, neck, antecubital and popliteal folds. No adverseevents possibly related to infliximab were observed.DISCUSSIONTNF-alpha is a multifunctional cytokine thatregulates not only immune response andinflammation, but also tissue remodeling, keratinocytemotility, cell cycle and apoptosis, as well as basementmembrane components and matrix metalloproteases(12-13). Some evidence has suggested the relationshipbetween TNF-alpha-308*2 polymorphism, which isassociated with the increased secretion and activity ofTNF-alpha, and the risk ofdeveloping asthma or atopybut there are still controversial data on this topic (14).Increased secretion ofTNF-alpha has been detected inthe respiratory tract of atopic asthmatics (15-16).The role of TNF-alpha in AD is still unknown,although it has been implicated in the expression ofadhesion molecules on both endothelia and keratinocytesin this disease (17-18). Determination of TNF-alphaplasma levels and production by mononuclear cells inAD patients gave controversial results (19-22). It shouldalso be mentioned that CD30, which is a marker ofTh2cell activation and whose soluble form is significantlyelevated in AD, belongs to the TNF-receptor family (23).Recently, it has been found that TNF-alpha is the maininducer of inducible protein-It), belonging to the CXCchemokine subfamily, by skin fibroblasts from patientswith atopic dermatitis (24).To our knowledge, the present case represents thefirst report of AD successfully treated with infliximab.On the contrary, there are reports of AD or AD-likeeruptions being associated with the use of infliximab oretanercept in patients with psoriasis, rheumatoidarthritis or juvenile idiopathic arthritis (6-8). Theseevents have been attributed to the shift towards apredominant Th2 response due to the downregulation ofThl cytokines caused by anti-TNF-alpha biologicals (8,25). Therefore, considering these reports, AD could notrepresent an indication for anti-TNF-alpha therapy,unlike conventional systemic immunomodulating drugswhich have proved effective in both psoriasis and AD,such as cyclosporin A (26-28). The results obtained inour case appear to suggest that there can be selectedsubgroups of AD patients who might benefit frominfliximab, although their discriminating characteristicsInt. J. Immunepathol, Pharmacol, 239are unknown. However, awaiting more precise data onthe mechanism of action of infliximab, we canhypothesize that the chronic-eontinuous and recalcitrantcourse ofAD, as confirmed by the psoriasiform patternon histology, and the concomitant contact dermatitis inour patient might have influenced a more preponderantTh l-mediated response than that expected in"common" forms of AD (29-34). Interestingly, someevidence supports the role of TNF-alpha in thepathogenesis of contact dermatitis (35-37).*NOTE: After the submission of this paper, astudy evaluating treatment with infliximab in atopicdermatitis has been published (Jacobi A. et al. 2005.J. Am. Acad. Dermatol. 52:522)REFERENCES1. Maini R., E.W. St Clair, F. Breedveld, D. Furst, J.Kalden, M. Weisman, J. Smolen, P. Emery, G.Harriman, F. Feldman and P. Lipsky. 1999.Infliximab (chimeric anti-tumour necrosis factoralphamonoclonal antibody) versus placebo in rheumatoidarthritis patients receiving concomitant methotrexate: arandomised phaseIII trial. Lancet 354:1932.2. Garnett W.R. and N. Yunker. 2001. Treatment ofCrohn's disease with infliximab. Am. J. Health Syst.Pharm.58:307.3. Chaudari U., P. Romano, L.D. Mulcahy, L.T.Dooley, D.G. Baker and A.B.Gottlieb. 2001.Efficacyand safety of infliximab monotherapy for plaque-typepsoriasis: a randomised trial. Lancet 357:1842.4. Antoni C. and B. Manger. 2002. 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Infliximab in recalcitrant severe atopic eczema associated with contact allergy.

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Infliximab in recalcitrant severe atopic eczema associated with contact allergy.

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