Pseudoporphyria Associated with Chronic Renal Failure: The Outcome from Oral N-Acetylcysteine Treatment in Three Cases

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1 OLGU SUNUMU Pseudoporphyria Associated with Chronic Renal Failure: The Outcome from Oral N-Acetylcysteine Treatment in Three Cases Simin ADA, MD, Assis.Prof., a Engin ŞENEL, MD, Msc b a Department of Dermatology, Başkent University Faculty of Medicine, Ankara b Dermatology Clinic, Çankırı State Hospital, Çankırı Ge liş Ta ri hi/re ce i ved: Ka bul Ta ri hi/ac cep ted: Ya zış ma Ad re si/cor res pon den ce: Simin ADA, MD, Assis.Prof. Başkent University Faculty of Medicine Department of Dermatology, Ankara, TÜRKİYE/TURKEY siminada@hotmail.com; siminada@baskent-ank.edu.tr ABS TRACT Pseudoporphyria is a rare and acquired bullous disorder with clinical and histopathological features identical to porphyria cutanea tarda, despite a normal porphyrin metabolism. It is associated with chronic renal failure, excessive sun exposure and various medications. There is no specific treatment for pseudoporphyria, but sun protection and discontinuation of the offending drugs may provide some benefit. Oral N-acetylcysteine has recently been reported as an effective treatment option in five cases in the literature. Here, we described our experience with N-acetylcysteine treatment in three patients with pseudoporphyria due to chronic renal failure. Key Words: Kidney failure, chronic; therapy; acetylcysteine ÖZET Psödoporfiri, klinik ve histopatolojik olarak porfiriya kutanea tardaya benzeyen, ancak porfirin metabolizmasının normal olduğu, nadir görülen, edinsel, büllöz bir deri hastalığıdır. Kronik böbrek yetmezliği, aşırı güneş maruziyeti ve çeşitli ilaçlarla ilişkilendirilmektedir. Psödoporfirinin spesifik bir tedavisi olmamakla birlikte, güneşten korunma ve sorumlu ilacın kesilmesi kısmi yarar sağlayabilmektedir. Literatürde, yakın zamanda beş olguda oral N-asetilsistein in etkili bir tedavi seçeneği olabileceği bildirilmiştir. Burada kronik böbrek yetmezliği zemininde gelişen üç psödoporfiri olgusunda oral N-asetilsistein tedavi deneyimimizi sunmaktayız. Anah tar Ke li me ler: Böbrek yetmezliği, kronik; tedavi; asetilsistein : doi: /medsci Cop yright 2012 by Tür ki ye Kli nik le ri seudoporphyria is a rare and acquired bullous disorder with clinical and histopathological features similar to those of porphyria cutanea tarda (PCT) despite a normal porphyrin metabolism. It is associated with chronic renal failure, excessive sun exposure and numerous medications such as furosemide, hydrochlorothiazide, tetracycline and naproxen. 1 So far, there has been no specific treatment for pseudoporphyria, although sun protection and discontinuation of the offending drugs may provide some benefit. Oral N-acetylcysteine has recently been reported as an effective treatment option in five cases. 2-6 This paper was aimed to share our experience on and present outcome of N-acetylcysteine treatment option in three pseudoporphyria patients associated with chronic renal failure. 1122

2 Dermatology and Venerology Ada et al. CA SE 1 CA SE RE PORTS A 38-ye ar-old wo man with chro nic re nal fa i lu re un der go ing he mo di aly sis 3 ti mes/we ek had a 2- month his tory of mul tip le ten se blis ters and ero si - ons with crus ting and at rop hic scars on her fa ce and dor sum of the hands (Fi gu re 1). Her me di cal his tory al so disc lo sed chro nic he pa ti tis C in fec ti on. Li ver func ti on tests and se rum fer ri tin le vels we re nor mal. CA SE 2 A 56-ye ar-old wo man pre sen ted a 2-we ek his tory of mul tip le ten se blis ters, ero ded and crus ted are as on her fa ce and dor sum of the hands (Fi gu re 2). She had be en un der go ing he mo di aly sis 3 ti mes/we ek for chro nic re nal fa i lu re for 7 ye ars. CA SE 3 A 72-ye ar-old wo man pre sen ted an 18-month history of mul tip le he morr ha gic blis ters on her ab do - men (Fi gu re 3) and dor sum of the hands. She had be en on he mo di aly sis 3 ti mes/we ek for chro nic re - nal fa i lu re for one ye ar. Her me di ca ti ons inc lu ded hydroch lo rot hi a zi de. His to pat ho lo gi cal exa mi na ti ons re ve a led su be - pi der mal bul la e in all pa ti ents (Fi gu re 4). Di rect immu nof lu o res cen ce stu di es of the pe ri le si o nal skin FIGURE 2: Case 2: Multiple tense blisters, eroded and crusted areas on the hands. FIGURE 3: Case 3: Multiple hemorrhagic blisters on the abdomen. FIGURE 1: Case 1: Multiple tense blisters and erosions with crusting and atrophic scars on the dorsum of the hands. FIGURE 4: Case 2: Histopatology of a blister from the dorsum of the hand showing subepidermal bullae (H&E, x10). 1123

3 Ada ve ark. we re ne ga ti ve. Uri ne uro porph yrin le vels we re wit hin nor mal li mits (nor mal, <25 μg/l). Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to excre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa - i lu re, the pa ti ents had not be en ab le to ex cre te eno - ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be perfor med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u - se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kidney fa i lu re, the pa ti ents had not be en ab le to ex cre - te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa i lu re, the pa ti - ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for - med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with Be ca u se of kid ney fa i lu re, the pa ti ents had not be en ab le to ex cre te eno ugh uri ne in the mor nings; thus the uri ne test co uld be per for med with nor mal. On the ba sis of cli ni co pat ho lo gi cal cor re la ti on and porph yrin da ta, all thre e pa ti ents we re di ag - no sed with pse u do porph yri a. Hydroch lo rot hi a zi de tre at ment was stop ped in the ca se 3 but its ces sa ti - on fa i led to re li e ve the le si ons. Oral N-acetylc yste - i ne (1,200 mg/day) tre at ment was ini ti a ted in ad di ti on to strict sun pro tec ti on by we a ring pro tecti ve clot hes, using bro ad-spec trum sun pro tec ti on fac tor 30 suns cre en and avo i ding di rect sun ex po - su re du ring day ti me. One month af ter chan ging the tre at ment, new bul la e de ve lop ment had stop - ped in the ca ses 1 and 3 and no furt her le si ons occur red du ring a 6-month fol low-up. Ho we ver, new Deri ve Zührevi Hastalıklar bul la e con ti nu ed to de ve lop in the ca se 2 des pi te in cre a sing the do se of N-acetylc yste i ne by half (1.800 mg/d). No ne of the pa ti ents comp la i ned abo - ut any si de ef fects of oral ad mi nis tra ti on of N- acetylc yste i ne. DIS CUS SI ON Porph yri as are cha rac te ri zed by ab nor ma li ti es in the he me bi osyn the tic path way. Porph yri a cu ta - ne a tar da is a pho to-in du ced blis te ring di sor der ca - u sed by an in he ri ted or ac qu i red de fi ci ency of uro porph yri no gen de car boxy la se, le a ding to ac cu - mu la ti on of porph yrins ma inly in uri ne but al so in sto ol and plas ma. Pa ti ents with PCT pre sent with skin fra gi lity and bul la for ma ti on which he al with mi li a and scar ring, most fre qu ently on pho to ex po - sed skin. Fa ci al hyper tric ho sis and hyper pig men - ta ti on are com mon. His to pat ho lo gi cally, su be pi der mal bul la e with clas sic fes to o ning of the der mal pa pil la e, thic ke ning of the der mal ves sel walls and der mal scle ro sis are ob ser ved. 7,8 Pse u do porph yri a is cli ni cally and his to lo gi - cally si mi lar to PCT, but typi cally lacks the bi oc - he mi cal ab nor ma li ti es. Both pse u do porph yri a and PCT may oc cur with in cre a sed fre qu ency among pa ti ents with chro nic re nal fa i lu re un der go ing hemo di aly sis. 9 It is im por tant to ma ke a comp le te porph yrin exa mi na ti on of uri ne, plas ma and sto ol to dis tin gu ish pse u do porph yri a from PCT. Ho we ver, this can be chal len ging es pe ci ally in the set ting of re nal fa i lu re and he mo di aly sis. Usu ally a mor ning uri ne samp le of 20 ml is analy zed for porph yrins, but du e to se ve re re nal fa i lu re and anu ri a, as in our ca ses, eno ugh amo unt of mor ning uri ne samp le may not be col lec ted. The re is al so di sag re e ment on whet her pse u do porph yri a has a comp le tely nor mal porph yrin pro fi le or may ha ve ele va ted plas ma porph yrins in the set ting of re nal fa i lu re Plas ma porph yrins may in cre a se be ca u se of im pa i red excre ti on of the se mo le cu les and inef fi ci ent cle a ran - ce by di aly sis sin ce porph yrins ha ve to o high mo le cu lar we ight to be cle a red by the he mo di aly - sis mem bra ne. Thus, it is bet ter to in ves ti ga te pa ti - ents porph yrin pro fi le by frac ti o na ti on of fe cal porph yrins. 13 Ho we ver, we we re unab le to per form fe cal porph yrin analy sis in our pa ti ents. 1124

4 Dermatology and Venerology The exact pat ho ge ne sis of pse u do porph yri a asso ci a ted with chro nic re nal fa i lu re is not fully cla r- i fi ed. Der mal mic ro an gi o pat hic chan ges and dec re a sed oxy ge na ti on du ring he mo di aly sis may faci li ta te fric ti o nal blis te ring. 14 He mo di aly sis pa ti ents are pro ne to oxi da ti ve stress and ha ve dec re a sed le - vels of glu tat hi o ne which is con si de red to be one of the most im por tant an ti o xi dant systems Ot her pro po sed fac tors trig ge ring pse u do porph yri a as so - ci a ted with he mo di aly sis inc lu de va ri o us drugs (di u re tics, alu mi num hydro xi de, ni fe di pi ne, ery tro - po e tin) he mo si de ro sis, and he pa ti tis C in fec ti on. 1 One of our ca ses al so had a chro nic he pa ti tis C infec ti on. It is well-known that chro nic he pa ti tis C in fec ti on is most fre qu ently as so ci a ted with PCT. 7,18 He pa ti tis C in fec ti on may trig ger sympto ma tic PCT in ge ne ti cally pre dis po sed pa ti ents. 19 Porph yrin analy sis exc lu ded a di ag no sis of PCT in our pa ti ent. We tho ught that hydroch lo rot hi a zi de tre at ment was a pos sib le trig ge ring fac tor in anot her pa ti ent. Ho we ver, it se ems un li kely that this drug was res - pon sib le alo ne for the pa ti ent s con di ti on be ca u se its ces sa ti on fa i led to cle ar the skin le si ons. Oral N-acetylc yste i ne, a synthe tic pre cur sor of re du ced glu tat hi o ne (GSH), is a thi ol-con ta i ning com po und that fa ci li ta tes in tra cel lu lar bi osyn the sis of glu tat hi o ne par ti cu larly in in cre a sed oxi da ti ve stress. 20 It can pre vent in cre a sed oxi da ti ve stress Ada et al. fol lo wing ad mi nis tra ti on of ra di o con trast agents and the re fo re has be co me wi dely used to pre vent con trast-in du ced nep hro pathy. Me anw hi le, N- acetylc yste i ne supp le men ta ti on has be en shown to be a pro mi sing the rapy for oxi da ti ve stres and re la - ted comp li ca ti ons inc lu ding car di o vas cu lar events in he mo di aly sis pa ti ents. 21,22 On the ba sis of its anti o xi dant pro per ti es and its abi lity to rep le nish dep le ted glu tat hi o ne le vels, oral N-acetylc yste i ne has re cently be en used to tre at 6 ca ses with he mo di - aly sis-as so ci a ted pse u do porph yri a, and has shown be ne fi ci al ef fect in fi ve of them. 2-6 Switch from low-flux to high-flux mem bra ne he mo di aly sis has al so be en used in com bi na ti on with N-acetylc yste - i ne in or der to pre vent re cur ren ce of blis te ring af - ter dis con ti nu a ti on of the drug in one of tho se ca ses. 4 We des cri be our ex pe ri en ce with oral N- acetylc yste i ne in furt her 3 ca ses of he mo di aly sisas so ci a ted pse u do porph yri a. 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