Palmoplantar pustulosis – is there any progress in the treatment? / Palmoplantarna pustuloza – ima li pomaka u lečenju?

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Abstract

Despite, the fact that palmoplantar pustulosis is still widely known by this name, it is currently regarded as a disease distinct from psoriasis. The real cause is still unknown. Septic foci have been blamed, but their removal may not cure eruptions. A case series of de novo occurrence of palmoplantar pustulosis induced by tumor necrosis factor-alpha antagonist therapy has been reported. It has been shown that stress may be related to exacerbation of palmoplantar pustulosis. Some authors suggest that palmoplantar pustulosis is an autoimmune disease. In sera of patients with palmoplantar pustulosis circulating autoantibodies against nicotinic acetylcholine receptors were detected. The differences between palmoplantar pustulosis and pustular palmoplantar psoriasis are numerous. Genetic studies have failed to find any link between palmoplantar pustulosis and major genetic susceptibility locus for psoriasis vulgaris. Most patients with palmoplantar pustulosis have no evidence of psoriasis elsewhere. Histologically, it closely resembles psoriasis. However, accumulation of neutrophils just beneath the corneal layer, finding known as Munro’s microabscess, and dilation of capillaries in the papillary dermis are lacking. Approximately 90% of patients are women. A significantly higher prevalence of smokers was found in the group with palmoplantar pustulosis than in the normal population and a particularly strong association was confirmed between smoking and pustular lesions in patients with psoriasis, OR=5.3 (2.1-13.0). Nevertheless, according to a recent review from the Cochrane Library, there is no evidence that smoking cessation improves the condition once it has developed.

Topical corticosteroids under occlusion are the first-line therapy. Prolonged therapy is needed on a second or third-day basis, in order to sustain the obtained effects. Oral retinoids in combination with oral PUVA are the best second-line therapy. No difference in the efficacy between etretinate and acitretin was found. The disadvantage of systemic retinoid therapy is its teratogenicity. Oral PUVA is effective and the response is enhanced by combination with retinoids. There is an established increased efficacy of a combination of retinoids with PUVA therapy over each treatment modallity when used alone. Liarozole may be an effective and well-tolerated therapy, but side effects are like in retinoids. The advantage over acitretin is that raised levels of retinoic acid fall to normal within a few days after cessation of therapy. Significant improvement, but no complete clearance, occurs in most patients treated with low dose cyclosporine. Before starting the treatment, it is necessary to consider: patient’s individual factors, since many patients have already received some previous treatment; specific treatment factors such as formulation, way of administration, dose, different drug combinations; regimens and periods of treatment; site of involvement, due to differences between hands and feet in the probability of response to treatment.

Sažetak

Definicija: Palmoplantarna pustuloza je hronična upalna bolest koju odlikuju eruptivne pustule na dlanovima i tabanima sa periodima egzacerbacije i parcijalne, retko potpune regresije.

Ne postoji opšta saglasnost da su palmoplantarna pustuloza i lokalizovana, palmoplantarna pustulozna psorijaza ista bolest. Iako je oboljenje poznato pod tim nazivom, palmoplantarna pustuloza se tek trenutno smatra posebnim, od psorijaze odvojenim entitetom.

Etiopatogeneza: Stvarni uzrok nastanka oboljenja nije utvrđen. Fokalne infekcije mogu biti prisutne ali se njihovom sanacijom ne postiže u svim slučajevima izlečenje. Opisani su de novo slučajevi u kojima je bolest nastupila u toku terapije antagonistima faktora nekroze tumora alfa. Pojedini slučajevi se mogu povezati sa stresom. Pojedini autori smatraju da je palmoplantarna pustuloza autoimuna bolest. U serumu obolelih otkrivena su antitela usmerena protiv nikotinskih acetilholinskih receptora. Ispitivanja su pokazala da je prevalencija pušača kod pacijenata sa palmoplantarnom pustulozom signifikantno viša od prevalencije u opštoj populaciji i da postoji visoko signitifikantna povezanost između pušenja i pustulozne psorijaze OR=5,3 (2,1−13). Ipak, ne postoje dokazi da prestanak pušenja dovodi do poboljšanja postojećih promena.

Odnos prema psorijazi: Razlike između palmoplantarne pustuloze i plamoplantarne pustulozne psorijaze su brojne. Nedavna genetska ispitivanja nisu utvrdila povezanost između palmoplantarne pustuloze i glavnog lokusa koji se dovodi u vezu sa povišenom genetskom predispozicijom za obolevanje od psorijaze. Većina pacijenata sa palmoplantarnom pustulozom nema psorijazu na drugom delu tela. Prevalencija psorijatičnih promena na udaljenim mestima varira počev od 2% preko 24% do 84%, od studije do studije. Žene obolevaju češće od muškaraca i čine 90% svih obolelih. Palmoplantarna pustuloza pokazuje visok stepen histološke podudarnosti sa psorijazom. Za razliku od psorijaze, kod palmoplantarne pustuloze ne dolazi do vazodilatacije kapilara u paplilarnom dermisu, niti akumulacije neutrofilnih granulocita neposredno ispod kornealnog sloja (Munro mikroapscesi).

Terapija: Lečenje palmoplantarne pustuloze je nezadovoljavajuće Mnogi medikamenti su primenjivani, a nijedan pouzdano ne suprimira bolest niti dovodi do izlečenja (katrani, topijski kortikosteriodi, ditranol, fotohemoterapija, oralni tetraciklini, metotreksat, retinoidi, lokalni ili sistemski, ciklosporin, kolhicin, biološka sredstva).

Lokalna primena kortikosteroida pod okluzijom, jedina je od lokalnih terapijskih procedura, koja se pokazala efikasnom za lečenje palmoplantarne pustuloze. Terapiju održavanja potrebno je sprovesti alternativnim nanošenjem leka svakog drugog/trećeg dana. Potrebne su dalje studije o efikasnosti ostalih preparata za lokalnu primenu.

Najbolji metod za lečenje palmoplantarne pustuloze u drugom terapijskom redu, predstavlja kombinacija sistemskih retinoida i sistemske (oralne) PUVA fotohemoterapije (Re-PUVA). Razlika u efikasnosti između etretinata i acitretina nije utvrđena. Manjkavost sistemske primene retinoida predstavlja opasnost od teratogenog efekta. Sistemskom PUVA terapijom postiže se dobar efekat ali se terapijska efikasnost signifikatno povećava u kombinaciji sa sistemskom primenom retinoida. Ova kombinacija se pokazala suverenom nad monoterapijom, kako u odnosu na PUVA tako i na retinoide.

Liarozole je imidazolski derivat a pripada novoj kategoriji lekova koji blokiraju metabolizam all-trans retinoične kiseline putem inhibicije enzima 4-hidroksilaze retinoične kiseline. Pokazao je efikasnost koja s jedne strane obećava ali istovremeno zahteva ozbiljnu proveru. Dobro se podnosi. Neželjena dejstva su kao i kod terapije sistemskim retinoidima, ali je njegova prednost u odnosu na acitretin to što se po prestanku primene lirazola, povišen nivo retinoične kiseline u serumu vraća na fiziološku vrednost u toku samo nekoliko dana.

Ciklosporin primenjen u niskim dozama (2 mg/kgTT dnevno) izaziva signifikantno poboljšanje ali ne i potpuno povlačenje promena.

Zaključak: Terapija treba da bude prilagođena svakom pojedincu, a to znači da je pre započinjanja lečenja potrebno razmotriti činioce kao što su: individualne osobine svakog pojedinog pacijenta, s obzirom da su mnogi pacijenti već prethodno lečeni; faktori specifični za odgovarajući metod lečenja, npr. način primene leka, koncentracija aktivne supstancije, doza, kombinovana primena dva ili više različita leka, različiti režimi u terapijskom pristupu, dužina lečenja; lokalizacija promena, s obzirom na razlike u terapijskom odgovoru između kože dlanova i tabana koje se mogu očekivati.

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Serbian Journal of Dermatology and Venereology

The Journal of Serbian Association of Dermatovenereologists (SAD)

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