Am J Clin Dermatol 2007; 8 (1): 47-50CASE REPORTS 1175-0561/07/0001-0047/$44.95/0

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Coexistent Psoriasis and Lupus ErythematosusTreated with AlefaceptCindy Berthelot,1 Jason Nash2 and Madeleine Duvic3

1 Department of Internal Medicine, University of Texas Houston Health Science Center, Houston, Texas, USA2 Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA3 Department of Dermatology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA

Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 471. Case Report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Coexistence of psoriasis and subacute cutaneous lupus erythematosus (SCLE) is unusual. Although thereAbstracthave been reports of this occurrence, there have been no reports of this overlap syndrome treated withimmunomodulators. We describe a case of coexisting psoriasis and SCLE initially treated with infliximab, andthen alefacept. The patient’s arthritis flared after the second infusion of infliximab, which was discontinued.During treatment with alefacept, the patient’s psoriasis improved markedly without exacerbation of hisphotosensitive SCLE lesions.

The combination of psoriasis and subacute cutaneous lupus family histories were negative for psoriasis and connective tissueerythematosus (SCLE) is rare. Making the diagnosis is often diseases. He was initially evaluated at the M.D. Anderson Cancerdifficult and relies on clinical findings, serologic studies, and Center (Houston, TX, USA) in October 2002 for a presumptivehistopathologic findings.[1] We report a case of a middle-aged man diagnosis of mycosis fungoides variant of cutaneous T-cell lym-with psoriasis and SCLE who received infliximab followed by phoma (CTCL).alefacept. While receiving infliximab, the patient’s arthritis flared Examination revealed erythematous, well demarcated, guttate,after the second infusion, and the drug was discontinued. While scaly psoriasiform plaques on the back, scalp, neck, extensorreceiving alefacept, the patient’s psoriasis improved markedly surface of the knees, and elbows. He also had a photo-distributedwithout exacerbation of his photosensitive SCLE lesions. macular eruption, most prominent on his face, which worsened

after sun exposure (figure 1). There was significant keratoderma1. Case Report blennorrhagica of his hands and feet. The plaques on his arms were

confluent, with sparing underneath his watchband. Cervical andIn June 2002 a 39-year-old White man developed a rapidlyoccipital lymphadenopathy were present.progressive, scaling rash that initially began on his face and then

generalized. Concomitantly, he developed severe arthritis in his A subsequent work-up for CTCL was negative, including skinhands, knees, and ankles. He also reported multiple constitutional biopsies with six negative T-cell gene rearrangements, and asymptoms, including weight loss of 20lb (9.1kg) in 6 weeks, normal blood and lymph node flow cytometry. Laboratory datafatigue, fever, nausea, and shortness of breath. The patient and revealed a positive anti-nuclear antibody (ANA) of 1 : 160 with a

48 Berthelot et al.

tion persisted and hydroxychloroquine 200 mg/day was started inSeptember 2004 for the SCLE. In May 2005, the patient presentedwith pulmonary emboli of the right and left lower lobes, and wasstarted on enoxaparin and warfarin. Lupus anticoagulant waspositive and factor Leiden mutation was not found.

2. Discussion

This patient presented with a psoriasiform papulosquamouseruption, initially diagnosed as mycosis fungoides. However, theReiter-like features, acral-extensor distribution, lack of lympho-cyte atypia or T-cell receptor clonality, as well as the spondyloar-thropathy, were more consistent with psoriasis. In addition, he hadsevere photosensitivity, positive ANA, a positive lupus band test(IgG distributed along the dermal epidermal junction), and a

Fig. 1. Photo-distributed macular eruption, consistent with subacute cuta-neous lupus erythematosus.

positive lupus anticoagulant. The patient was treated with metho-trexate for several months without benefit and flared on inflix-speckled pattern. Anti-Ro/La, complement levels, erythrocyte sed-imab, which is characteristic of lupus. Fortunately, both theimentation rate, Sjogren antibody, and double-stranded DNA werepsoriasis lesions and the SCLE responded to serial use of alefaceptall within normal limits. Rapid plasma reagin, HIV, and HLA-B27and hydroxychloroquine.were all negative. A chest x-ray was negative and a CT scan of the

Because an ANA is nonspecific and a positive immunofluores-chest revealed small, scattered lymphadenopathy of the neck. Acence on sun-exposed skin may occur in individuals who arecervical lymph node biopsy showed reactivity without lymphoma.otherwise healthy or have facial dermatoses, including seborrhea,The CT scan of the abdomen was normal.the possibility that the patient’s diagnosis was SCLE alone wasA skin biopsy of the psoriatic lesions performed in Octoberconsidered. However, the clinical lesions of keratoderma blennor-2002 was consistent with treated psoriasiform dermatitis withrhagica, the plaques on the elbows and knees, and the severe spinaloverlying confluent parakeratotic scale (figure 2). The epidermisarthritis favored the diagnosis of psoriasis while the serology,was acanthotic with some spongiosis and intraepithelial lympho-photosensitivity, and lupus anticoagulant supported the two diag-cytes without any evidence of atypia. The papillary dermis showednoses of coexistent psoriasis and SCLE. Both psoriasis and SCLEectatic venules surrounded by a predominantly lymphocytic infil-(and mycosis fungoides) can have lesions that are papulosqua-trate involving the superficial plexus. Immunofluorescence of amous in appearance. Coexistence of psoriasis and SCLE is rare,facial lesion skin biopsy showed granular IgG at the dermal-occurring in 0.69% of patients with psoriasis and 1.1% of thoseepidermal junction, consistent with LE. Therefore, psoriasis-

SCLE overlap syndrome was diagnosed.

Methotrexate 15 mg/week was given for 1 month withoutimprovement. Infliximab 3 mg/kg was started in November 2002,then increased to 5 mg/kg. The patient reported improvement ofhis arthritis, and clearing of his psoriatic lesions without improve-ment of his SCLE. Five days after the second dose of infliximab,the patient developed a severe exacerbation of his arthritis requir-ing hospitalization. This was thought to be due to infliximab,which was discontinued. Methotrexate was restarted in December2002 at 15 mg/week then increased to 25 mg/week; however, thepatient’s lesions did not improve after several months’ therapy.Intramuscular alefacept 15 mg/week was started in April 2003 andthe patient received a total of five courses with clearing of allpsoriatic lesions. However, the scaly facial rash in a photodistribu-

Fig. 2. Psoriasiform dermatitis with acanthotic epidermis, spongiosis, hy-perkeratosis, and perivascular lymphocytes without atypia (×100).

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (1)

Coexistent Psoriasis and Lupus Erythematosus Treated with Alefacept 49

with LE.[2] The mechanism of interaction between these two duced lupus in association with anti-TNF therapy remains a con-diseases is unclear; however, immunologic dysregulation and T- cern and cases have been described.[17,18] One study revealed 22cell stimulation through superantigens may be the common cases of drug-induced lupus (15 patients received infliximab andmediators of these disorders.[3-5] There is no specific serologic seven patients received etanercept).[19] Because it is a fully humanmarker for their coexistence. One study suggested that anti-Ro fusion protein, alefacept may avoid the induction of autoantibo-antibodies may be a specific marker for psoriasis-LE overlap.[6] dies, and may therefore be safely administered in patients withAntibodies to Ro in this study were absent in 24 control patients psoriasis-SCLE overlap.with psoriasis, as in our patient. All four patients in a second study

3. Conclusionhad high ANAs and negative anti-Ro antibody.[7] The authorsconcluded that anti-Ro antibody may not be a specific marker for

The coexistence of psoriasis and SCLE is rare and posesthe coexistence of psoriasis and LE. Although the presence of anti-

challenges in the selection of appropriate treatment. ExacerbationRo antibody is variable, there is consensus that photosensitivity,

of SCLE may occur with infliximab; however, our patient’swhich was present in our patient, may be noted in approximately

psoriasis improved markedly with alefacept without flaring of his50% of patients with psoriasis-LE overlap.[6,8,9] In one study, 20 of

photosensitive SCLE lesions. As more experience is gathered, the27 patients (74%) had morphologically distinct lesions of psoriasis

role of alefacept and other immunomodulators in the managementand LE.[8] As with our patient, the onset of psoriasis preceded that

of psoriasis-SCLE overlap will be clarified.of LE in approximately 50% of cases.[5]

The coexistence of psoriasis and LE poses challenges in choos- Acknowledgmentsing appropriate treatment. Psoriasis is traditionally treated with

This study was funded in part by the National Institute of Arthritis andphototherapy; however, in overlap patients, this may exacerbateMusculoskeletal and Skin Diseases K24-CA86815 (MD) and by the Sherry L.their disease. On the other hand, certain drugs used to treat LE,Anderson CTCL Patient Research Fund. The authors have no conflicts of

such as antimalarials, have been associated with psoriasisinterest that are directly relevant to the content of this study.

flares.[10]

Alefacept is a fully human fusion protein that selectively targets Referencesmemory T cells, and is approved by the US FDA for the treatment 1. Wohl Y, Brenner S. Cutaneous LE or psoriasis: a tricky differential diagnosis.

Lupus 2004; 13 (1): 72-4of moderate-to-severe chronic plaque psoriasis. It is well tolerated2. Zalla MJ, Muller SA. The coexistence of psoriasis with lupus erythematosus andand demonstrates no evidence of increased risk of infections or

other photosensitive disorders. Acta Derm Venereol Suppl (Stockh) 1996; 195:malignancies.[11,12] Unlike other immunomodulators, alefacept has 1-15

3. Ferahbas A, Utas S, Canoz O, et al. The coexistence of subacute cutaneous lupusa low incidence of immunogenicity with no evidence of an in-erythematosus and psoriasis. J Eur Acad Dermatol Venereol 2004 May; 18 (3):

creased rate of antibody development.[11] In contrast, infliximab, a 390-14. Baselga E, Puig L, Llobet J, et al. Linear psoriasis associated with systemic lupuschimeric IgG1 monoclonal antibody that specifically binds to

erythematosus. J Am Acad Dermatol 1994 Jan; 30 (1): 130-3human tumor necrosis factor (TNF)-α, has been shown to worsen5. Hu CH, O’Connell BM, Farber EM. Coexistent psoriasis and lupus erythematosus:

pre-existing LE.[13] This raises the question of whether LE is a what’s happening? Cutis 1985 Dec; 36 (6): 449-506. Kulick KB, Mogavero Jr H, Provost TT, et al. Serologic studies in patients withrelative contraindication for anti-TNF therapy.[14] The main con-

lupus erythematosus and psoriasis. J Am Acad Dermatol 1983 May; 8 (5):cern of infliximab therapy in patients with LE is induction of 631-4

7. Hays SB, Camisa C, Luzar MJ. The coexistence of systemic lupus erythematosusANA, anti-double stranded DNA, and anti-cardiolipin antibo-and psoriasis. J Am Acad Dermatol 1984 Apr; 10 (4): 619-22dies.[15] One open-label study of six patients with LE examined the

8. Millns JL, Muller SA. The coexistence of psoriasis and lupus erythematosus: ansafety and efficacy of infliximab in these patients.[16] Although analysis of 27 cases. Arch Dermatol 1980 Jun; 116 (6): 658-63

9. Lynch WS, Roenigk Jr HH. Lupus erythematosus and psoriasis vulgaris. Cutisinfliximab did not lead to increased LE activity, levels of antibo-1978 Apr; 21 (4): 511-6, 523-5

dies to double-stranded DNA and cardiolipin increased in four 10. Kontochristopoulos GJ, Giannadaki M, Doulaveri G, et al. Psoriasis coexistingwith subacute cutaneous lupus erythematosus. J Eur Acad Dermatol Venereolpatients each. In addition, all three patients with prior arthritis2004 May; 18 (3): 385-6experienced a flare of their arthritis 8–11 weeks after their last

11. Liu CM, McKenna JK, Krueger GG. Alefacept: a novel biologic in the treatment ofinfliximab infusion.[16] Our patients’ psoriasis and arthritis initially psoriasis. Drugs Today (Barc) 2004 Dec; 40 (12): 961-74

12. Gottlieb AB. Alefacept is well tolerated in patients with chronic plaque psoriasis.improved with infliximab; however, his arthritis was severelyJ Cutan Med Surg 2004 Dec; 8 Suppl. 2: 14-9

exacerbated after the second infusion, which raises the concern of 13. Weinberg JM. An overview of infliximab, etanercept, efalizumab, and alefacept asaggravation of his SCLE. In addition, development of drug-in- biologic therapy for psoriasis. Clin Ther 2003 Oct; 25 (10): 2487-505

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50 Berthelot et al.

14. Vabre-Latre CM, Bayle P, Marguery MC, et al. Worsening of subacute lupus 18. High WA, Muldrow ME, Fitzpatrick JE. Cutaneous lupus erythematosus inducederythematosus induced by infliximab. Ann Dermatol Venereol 2005 Apr; 132 by infliximab [letter]. J Am Acad Dermatol 2005 Apr; 52 (4): E5(4): 349-53 19. De Bandt M, Sibilia J, Le Loet X, et al. Systemic lupus erythematosus induced by

15. Aringer M, Smolen JS. SLE-complex cytokine effects in a complex autoimmune anti-tumour necrosis factor alpha therapy: a French national survey. Arthritisdisease: tumor necrosis factor in systemic lupus erythematosus. Arthritis Res Res Ther 2005; 7 (3): R545-51Ther 2003; 5 (4): 172-7

16. Aringer M, Graninger WB, Steiner G, et al. Safety and efficacy of tumor necrosisfactor alpha blockade in systemic lupus erythematosus: an open-label study. Correspondence and offprints: Prof. Madeleine Duvic, Department of Der-Arthritis Rheum 2004 Oct; 50 (10): 3161-9

matology, University of Texas M.D. Anderson Cancer Center, 1515 Hol-17. Shakoor N, Michalska M, Harris CA, et al. Drug-induced systemic lupus er-combe Boulevard, Box 434, Houston, TX 77030–4009, USA.ythematosus associated with etanercept therapy. Lancet 2002 Feb 16; 359

(9306): 579-80 E-mail: mduvic@mdanderson.org

© 2007 Adis Data Information BV. All rights reserved. Am J Clin Dermatol 2007; 8 (1)