Introduction 14 3 13 15 2 12 Cases and discussion 1 1 Table 1 Description of cases Case 1 2 3 4 5 Sex Male Male Female Female Male Age 37 42 67 30 41 Disease duration (years) 17  28 30 Unknown 15 Psoriasis type Plaque Plaque Plaque Plaque Plaque Prior pustular psoriasis No No No No No Psoriatic arthritis Yes No No No Yes Familiy history of psoriasis Negative Positive Negative Unknown Negative Prior UV-therapy Yes Yes Yes Yes Yes Prior systemic therapies     Fumaric acid esters      Initial response to infliximab c f PASI 75 PASI 75 PASI 75 Time of manifestation of PPP d 8 weeks after end of infliximab treatment d d d a Yes Yes No No Yes Development of GPP in addition to PPP Yes No No No No Potential trigger factors of PPP  Infection prior to PPP Yes No Yes No No  Present smoking No No Yes (36 packyears) Unknown Unknown Discontinuation of infliximab Yes Yes Yes No Yes b Adalimumab 40 mg e.o.w Etanercept 25 mg BIW plus methotrexate 7.5 mg/week orally PUVA-therapy of palms and soles (Additional topical therapy) Etanercept 50 mg BIW Systemic therapy that failed to control PV or PPP e    Etanercept 25 mg BIW PPP GPP PV e.o.w a  b  c  d  e  f  Fig. 1 a b c d  1 6 11 16 19 4 8 10 16 11 In two of the three cases in whom an exacerbation of plaque-psoriasis occurred parallel to the manifestation of PPP, typical trigger factors for active psoriasis could be identified such as an infection (case 3) and the abrupt termination of anti-psoriatic treatment (case 2). These two cases are compatible with the existence of common trigger factors for plaque psoriasis and PPP. What are other factors that might contribute to the development of PPP during treatment of psoriasis vulgaris? While the exact etiology of PPP remains to be established, a history of smoking is the most important known risk factor for PPP. However, only one out of the three patients in whom a smoking history had been obtained was a smoker at the time of onset of pustular psoriasis (case 3). Streptococcal infection, a known risk factor for psoriasis vulgaris, has not been established as a risk factor for PPP and probably plays a minor role there. However, in the cases presented here, one patient (case 3) suffered an upper respiratory tract infection a few days before manifestation of PPP, while another patient (case 1) had suffered from a persistent cold 6 weeks before manifestation of pustules. In the former patient, the close temporal relationship between infectious symptoms and manifestation of PPP may point to a possible contribution of the infection to triggering PPP, and a modulation of the immune response to infliximab appears possible. 7 6 PSORS1 2 11 5 6 16 The treatment of patients with plaque-psoriasis developing PPP should be decided on an individual basis. In case plaque-psoriasis remains controlled under infliximab therapy, addition of topical therapy may be sufficient for treatment of PPP in some instances (case 4). However, in some cases, additional topical therapy may not be sufficient and UV-therapy or another systemic therapy may be necessary in addition to or as replacement of infliximab therapy (case 3). When manifestation of PPP is accompanied by worsening of plaque-psoriasis, discontinuation of infliximab therapy is advisable and initiation of other systemic antipsoriatic agents, such as cyclosporine or a different TNF-antagonist, may be necessary (cases 1 and 5). In summary, pustular psoriasis may show a good response to treatment with TNF-antagonists such as infliximab. However, pustular psoriasis may also manifest during treatment of rheumatological diseases, and, as described here, also in patients with plaque-type psoriasis under treatment with infliximab. Manifestation of PPP under infliximab is not necessarily accompanied by worsening of pre-existing plaque psoriasis. Management of the pustular skin lesions has to be decided on an individual basis. In a subgroup of patients, therapy with the TNF-antagonist has to be discontinued and another systemic therapy (including a different TNF-antagonist) will probably be necessary to sufficiently control plaque-psoriasis and PPP.