Clinical dermatology • Concise report

CED

Clinical and Experimental Dermatology

Generalized pustular psoriasis associated with Epstein–Barr virus Z. Jiyad, B. Moriarty, D. Creamer and E. Higgins Department of Dermatology, King’s College Hospital, London, UK doi:10.1111/ced.12493

Summary

Generalized pustular psoriasis (GPP) is a rare and severe variant of psoriasis. We report a case of a 79-year-old woman who presented with generalized pustular psoriasis and significant Epstein–Barr virus (EBV) viraemia. Serial measurements of EBV DNA showed a correlation with the deterioration in her clinical condition. We speculate that EBV reactivation triggered the development of GPP, and propose that further investigation is required into the association between EBV and GPP.

Generalized pustular psoriasis (GPP) is characterized by macular erythema with sterile pustules. Recognised triggers include pregnancy and rapid tapering of steroids. The aetiology of generalized pustular psoriasis (GPP) is yet to be fully understood. We report a case of GPP associated with Epstein–Barr virus (EBV).

Report A 79-year-old woman presented with a 9-day history of a pustular eruption affecting her trunk and limbs, associated with malaise and fever (Fig. 1). She had no medical comorbidities, and no personal or family history of cutaneous disease. Four weeks previously, she had developed periungal erythema and pustulation of her left great toe, for which she had been treated unsuccessfully with combination oral and topical antibiotics by her general practitioner. Six days prior to our review, she had been started on prednisolone 30 mg after presenting to the emergency services. On physical examination, confluent erythema was seen, affecting 90% of the patient’s body surface area, and studded with sheets of monomorphic pustules, which coalesced into an annular configuration in some areas. She had a fever of 38.4 °C, and sinus tachycardia with a pulse rate of 100 beats/min. Full blood count and biochemical analysis identified Correspondence: Dr Zainab Jiyad, Department of Dermatology, King’s College Hospital, London, SE5 9RS, UK E-mail:[email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 31 March 2014

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neutrophil leucocytosis with white cell count of 19.38 9 109/L (normal range 4–11 9 109/L), neutrophils 15.95 9 109/L (2.5–7.5 9 109/L) and elevated C-reactive protein of 130.4 mg/L (< 10 mg/L). Histological examination of a skin biopsy demonstrated acute on chronic inflammation and psoriasiform epidermal hyperplasia, with large subcorneal pustules and extensive neutrophil exocytosis (Fig. 2). Liver tests were minimally deranged, with alkaline phosphatase at 139 U/L (normal range 45–105 U/L) and c-glutamyl transferase at 78 U/L (4–35 U/L). Viral screen was positive for EBV viral capsid antigen (VCA) IgG, and Epstein–Barr nuclear antigen (EBNA)-1 IgG, and negative for EBV VCA IgM (Liaison; DiaSorin, Saluggia, Italy). Significant EBV viraemia with EBV viral load of 59 920 copies/mL was detected (on the day of admission on 27 February). Screening for other infectious agents including hepatitis A, B and C, cytomegalovirus, Mycoplasma, and Streptococcus were negative. Further investigations into the patient’s immune status showed normal paraprotein and immunoglobulin levels, and an HIV test was negative. Acute generalized exanthematous pustulosis was excluded, and a diagnosis of GPP, with acrodermatitis continua of Hallapeau of the left great toe was made. The patient was admitted to hospital for stabilization and intensive topical therapy. Methotrexate was initiated at a starting dose of 2.5 mg. The patient was discharged 7 days later, much improved. Her EBV DNA viral load had decreased to 4515 copies/mL (4 March). She made a complete recovery over the following 6 weeks, apart from a relapse 2 weeks after discharge, which was characterized by temporary

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Generalized pustular psoriasis associated with EBV  Z. Jiyad et al.

EBV DNA

140 000 120 000

EBV copies/mL

100 000 80 000 60 000 40 000 20 000 0 27-Feb

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Figure 1 Widespread pustular erythema, with annular configura-

tion seen on the left.

CRP mg/L

250 200 150 100 50 0 27-Feb

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Body surface area 100%

80%

BSA %

60%

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0% 27-Feb

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Figure 2 Several large, mainly subcorneal, collections of neu-

Figure 3 Epstein–Barr virus (EBV) DNA (copies/mL), C-reactive

trophils within the epidermis, together with extensive neutrophil exocytosis. The upper dermis shows some dilated blood vessels, together with a mild, mixed, acute and chronic inflammatory cell infiltrate.

protein (CRP; mg/L) and percentage body surface area (BSA) involved. Note the rise in CRP correlating with peaks in EBV DNA and progression of skin involvement. This occurred on admission, and a second peak occurred after the initiation of methotrexate.

extension of erythema, development of new pustules and malaise. Her blood tests at that time showed a rise in EBV viral load, mirroring her clinical deterioration (Fig. 3). GPP is characterized by confluent macular erythema with sterile pustules, reflecting the neutrophilic infiltration seen histologically. Triggering factors include pregnancy, rapid tapering of corticosteroids, and hypocalcaemia.1 A bacterial trigger, Streptococcus pyogenes, has been demonstrated in guttate psoriasis, but not in pustular disease.2 Although viral triggers have been implicated in psoriasis, a causative relationship has not been established. Yoneda et al.3 reported two cases of GPP

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associated with cytomegalovirus (CMV) infection, suggesting that CMV-related activation of tumour necrosis factor-a and interleukin-6 might precipitate the eruption. Weitz et al.4 demonstrated that psoriasis was more severe in CMV-seropositive patients, and that the severity positively correlated with the degree of CMV antigenaemia. EBV infection has been reported to trigger guttate psoriasis.5 Loh reported a case of a 15-year-old girl with symptoms of glandular fever preceding the emergence of guttate psoriasis by 3 weeks. In that case, there was serological evidence of recent infection with a positive EBV IgM.

Clinical and Experimental Dermatology (2015) 40, pp146–148

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Generalized pustular psoriasis associated with EBV  Z. Jiyad et al.

EBV is a herpesvirus carried by 90% of the population worldwide, and it generally persists throughout life without causing disease.6 Positive VCA IgM and IgG in the absence of EBNA-1 IgG are typically found in patients with primary infections, whereas the presence of EBNA-1 IgG and absence of EBNA-1 IgM denotes previous infection, as in our patient.7 Our patient had significant EBV viraemia, which coincided with the onset of GPP, and mirrored the clinical course of the illness. Asymptomatic EBV reactivation may occur in many clinical contexts in an unwell host. Methotrexate-related immunosuppression may also reactivate EBV, and may have been a factor in the second EBV DNA peak our patient; however, she had a documented viraemia prior to commencing the drug.8 We speculate that EBV reactivation may have triggered the development of GPP in our patient, and propose that EBV serology should form part of the standard investigation set for all patients presenting with new-onset pustular psoriasis. It is possible that there may be an avenue for treatment with antivirals, but further research is required.

Learning points • EBV is a herpesvirus carried by 90% of the pop-

References 1 Van de Kerkhof PCM, Nestle FO. Psoriasis. In: Dermatology, 3rd edn (Bolognia JL, Jorizzo JL, Schaffer JV, eds). Philadelphia: Elsevier Saunders, 2012; 140–141. 2 Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection in the initiation of guttate psoriasis. Arch Dermatol 1992; 128: 39–42. 3 Yoneda K, Matsuoka-Shirahige Y, Demitsu T, Kubota Y. Pustular psoriasis precipitated by cytomegalovirus infection. Br J Dermatol 2012; 167: 1186–9. 4 Weitz M, Kiessling C, Friedrich M et al. Persistent CMV infection correlates with disease activity and dominates the phenotype of peripheral CD8+ T cells in psoriasis. Exp Dermatol 2011; 20: 561–7. 5 Loh E, Fung MA, Maverakis E. Acute guttate psoriasis in a 15-year-old girl with Epstein-Barr virus infection. Arch Dermatol 2012; 148: 658–9. 6 Puchhammer-St€ ockl E, G€ orzer I. Cytomegalovirus and Epstein-Barr virus subtypes – the search for clinical significance. J Clin Virol 2006; 36: 239–48. 7 Crowley A, Connell J, Schaffer K et al. Is there diagnostic value in detection of immunoglobulin g antibodies to the Epstein–Barr virus early antigen? Biores Open Access 2012; 1: 291–6. 8 Mariette X, Cazals-Hatem D, Warszawki J et al. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood 2002; 99: 3909–15.

ulation. • Reactivation of EBV can occur in an unwell or

immunosuppressed host. • EBV may play a role in precipitating pustular

psoriasis. • EBV serology should be performed in patients

presenting with new onset of pustular psoriasis.

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Generalized pustular psoriasis associated with Epstein-Barr virus.

Generalized pustular psoriasis (GPP) is a rare and severe variant of psoriasis. We report a case of a 79-year-old woman who presented with generalized...
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