Sonja Vesic

Herpes zoster as an immune restoration disease in AIDS patients during therapy including protease inhibitors.

A prospective study to evaluate the incidence of herpes zoster (HZ) as an immune restoration disease in patients with AIDS during highly active antiretroviral therapy (HAART) was conducted in a series of 115 patients diagnosed with AIDS initiated on HAART between 1 January 2000 and 31 July 2001. Of these, a single dermatomal HZ episode occurred in 14 (12%) patients within one and 15 months of HAART (median eight months). The HZ patients were similar to the non-HZ patients in age, sex, and HIV transmission risk factor, but had a more advanced disease. Compared with the baseline values, the viral loads significantly (P<0.01) decreased, while the mean CD4+ T-cell counts increased by almost four-fold (P<0.01) in both groups at the time of the HZ episode (or equivalent in non-HZ), but remained below 400/mL in the HZ patients. HZ during HAART is an immunopathological consequence of the improvement of the host immune response, correlating with the beginning of immune restoration.

Preparation of novel apigenin-enriched, liposomal and non-liposomal, antiinflammatory topical formulations as substitutes for corticosteroid therapy.

Two oil‐in‐water formulations, containing equal amounts of apigenin‐enriched chamomile flower extracts, for potential use as topical antiinflammatory agents, were prepared and their physicochemical properties evaluated. A pilot clinical study was then carried out to assess patient acceptability and efficacy. The creams were either non‐liposomal or liposomal. The liposomal formulations were more viscous, thus producing superior release characteristics in vitro. The clinical study also showed that the liposomal creams were, as antiinflammatory agents, slightly more effective in vivo than the non‐liposomal formulations. These results suggest that there is scope for the further development of even more effective and safer alternatives to corticosteroids. Copyright

Tufted hair folliculitis: A pattern of scarring alopecia?☆☆☆

We present a patient with pemphigus vulgaris who, over the years, experienced the development of tufted hair folliculitis as a result of scalp involvement. Multiple hairs emerged from widely dilated follicular ostia surrounded by indurated, scarred skin. Histopathologic findings were typical for tufted hair folliculitis. We believe that because a specific host response to scalp injury might be crucial to the development of this rare disorder, it should be regarded as a type of scarring alopecia.

Pseudoepitheliomatous, Keratotic and Micaceous Balanitis

A case of pseudoepitheliomatous, keratotic and micaceous balanitis (PEKMB) in a 64-year old man is presented. The patient presented with the 2-year history of a slowly enlarging, hyperkeratotic plaque

Dexamethasone-cyclophosphamide pulse therapy in pemphigus: a review of 72 cases.

AbstractBackground: Autoimmune pemphigus is a group of severe blistering diseases. Although corticosteroids have dramatically altered the prognosis of pemphigus, morbidity and mortality resulting from the adverse effects of systemic corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy was introduced to diminish the adverse effects of prolonged conventional daily dose regimens. Objective: To report our experience with the use of the DCP regimen in patients with autoimmune pemphigus. Methods: In the period 1998–2002, 72 patients with various forms of autoimmune pemphigus treated with DCP therapy were included, of whom 36 patients were previously treated with conventional corticosteroid therapy, and 36 were newly diagnosed patients. Results: Of the 72 patients, 43 completed treatment, while 13 patients did not respond adequately to the treatment and continued with the conventional daily regimen, nine patients were lost to follow-up, and seven patients died. Two of these deaths were probably a consequence of DCP therapy. Conclusion: DCP regimen is a beneficial treatment for patients with pemphigus, sparing the adverse effects of conventional regimens.

Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based cross-sectional study

BACKGROUND Emerging epidemiological evidence suggests independent associations between psoriasis and metabolic syndrome. Objectives: The aim of the study was to examine the prevalence of metabolic syndrome and its components in patients with psoriasis, and to assess which factors may predict metabolic syndrome in these patients. METHODS A hospital-based, cross-sectional study with 244 psoriatic patients and 163 control subjects with skin diseases other than psoriasis was conducted at the Clinic of Dermatovenerology, Clinical Center of Serbia, Belgrade, from October 2011 to October 2012. Metabolic syndrome was defined using the revised National Cholesterol Education Program Adult Treatment Panel III. Severity of psoriasis was measured by Psoriasis Area and Severity Index and Body Surface Area. RESULTS The adjusted odds ratios (ORs) and 95% confidence intervals (CI) for psoriasis patients vs. non-psoriasis patients were 2.66 (95% CI, 1.58-4.42) for metabolic syndrome, 3.81 (95% CI, 2.30-6.31) for hypertension, 2.29 (95% CI, 1.39-3.78) for central obesity, 1.92 (95% CI, 1.08-3.41) for hyperglycemia, 1.87 (95% CI 1.18-2.96) for low high-density lipoprotein cholesterol level, and 1.42 (95% CI, 0.87-1.04) for hypertrigliceridemia. We failed to find any statistically significant association between the metabolic syndrome and clinical severity of psoriasis. Later onset and longer duration of psoriasis were predicting factors for metabolic syndrome in our patients. Study limitations: The cross-sectional design of the study does not allow us to draw directional causal inferences concerning the association between psoriasis and metabolic syndrome. Factors such as diet, alcohol consumption or mental health, which have not been evaluated in this study, may be confounders in this relation. CONCLUSION A higher prevalence of metabolic syndrome and its components in patients with psoriasis than in controls, regardless of disease severity, emphasizes the need for early treatment and follow-up of all psoriatic patients with respect to metabolic diseases.

Effect of small changes in natural origin-based emulsion systems on hydrocortisone skin absorption and performance: a comparison of two in vivo methods

Abstract Context: Alkyl polyglucoside surfactants (APG) remain prominent natural origin stabilizers offering a prospect of combining satisfactory stability with mild dermatological properties and complete biodegradability. Objective: With the purpose of adjusting the dose to a patient’s needs, dilution of commercial corticosteroid formulations is a practice which may modify efficacy uncontrolledly. The rational of the study was to investigate whether a simple change in ready-to-use bases (co-solvent addition) could address these needs in a more predictive manner. Methods: Hydrocortisone (HC) delivery from such emulsion systems was comparatively assessed employing two in vivo methods: the established human skin blanching assay versus skin stripping technique. Results: HC permeation data obtained after three dose durations showed better overall performance of the APG-stabilized bases relative to reference ones. Although the solubility study showed that all the assessed active samples retained equal thermodynamic activity, diverse HC permeation/penetration implies the importance of the applied base’s colloidal structure and/or changes endured. Isopropyl alcohol (IPA) addition offered faster drug penetration enhancement, while glycerol as a moisturizing agent influenced HC penetration through the increase in skin hydration. Conclusion: Although the performed in vivo methods cannot be considered alternative, skin stripping technique proved to be a cost-efficient mode of percutaneous penetration assessment, providing additional information on vehicle–skin interactions.

Pyoderma vegetans in a patient with myelodysplastic syndrome

References 1 Livinghood CS, Rogers AM, Fitz-Hugh T. Dhobi mark dermatitis. J Am Med Assoc 1943; 123: 23–26. 2 Walker SL, Lear JT, Beck MH. Toxicodendron dermatitis in the UK. Int J Dermatol 2006; 45: 810–813. 3 Fisher AA, Mitchell JC. Allergic sensitization to plants. In: Rietschel RL, Fowler JF Jr, eds. Fisher’s Contact Dermatitis, 5th edn. Philadelphia, PA: Lippincott Williams & Wilkins, 2001: 351–395. 4 Kligman AM. Poison ivy (rhus) dermatitis. Arch Dermatol 1958; 77: 149–180. 5 James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin, Clinical Dermatology, 10th edn. Philadelphia, PA: Elsevier, 2006: 97–98. 6 Guin JD. The black spot test for recognizing poison ivy and related species. J Am Acad Dermatol 1980; 2: 332–333. 7 Ducombs G, Schmidt RJ. Plants and plant products. In: Rycroft RJG, Menne T, Frosch PJ, et al., eds. Textbook of Contact Dermatitis, 3rd edn. Berlin: Springer, 2001: 885–931.

Objective skin performance evaluation: How mild are APGs to the skin?

Abstract: Emulsion systems are the most common vehicles for topical drugs/cosmetic actives. Absence of skin irritation potential is an important legislative requirement. Overcoming emulsion irritancy is usually achieved by selection of emulsifiers. Alkyl Polyglucoside (APG) emulsifiers, successfully used in cosmetics and popularly labelled as skin- and environmentally friendly, have attracted considerable interest. Non-invasive measurements of biophysical skin parameters, and approved in vitro methods, are used for reliable and objective determination of skin properties. This chapter discusses assessment of the performance of topical emulsions, particularly those based on APG-mixed emulsifiers, and interpretation of the results. Research into the safety and efficacy of APGs indicates that APG surfactants could be used for tailoring mild emulsion vehicles, showing benefits as carriers for actives with an unfavourable skin irritation profile.

Lisinopril-Induced Pemphigus Foliaceus in a Patient with Diabetes Mellitus and Kaposi-Juliusberg Varicelliform Eruption

Abstract Drugs have often been implicated as the cause of pemphigus. Lisinopril is a drug of the angiotensin-converting enzyme inhibitor class primarily used in the treatment of hypertension, congestive heart failure, heart attacks, and also in preventing renal and retinal complications of diabetes mellitus. Various side-effects have been described in the English medical literature related to lisinopril, but only one case with pemphigus foliaceus as an adverse reaction to lisinopril. To the best of our knowledge, we present the second case of lisinopril-induced pemphigus foliaceus complicated with Kaposi-Juliusberg varicelliform eruption in a patient diabetes mellitus type II. A 60-year-old man presented with diffuse erythema on the face, trunk and extremities. Disseminated erosions, 2-5 mm in diameter, and umbilicated vesicles were present. Erosions with remnants of the blister roof were partially found on the trunk. Semiannular erosions were present. On the posterior part of the trunk (paravertebral and vertebral) there were inifiltrated, partially grouped, sharply delineated yellowish-reddish plaques, up to 2 cm in diameter. Direct and indirect immunofluorescence test as well as histological analysis revealed a drug-induced pemphigus foliaceus. After treatment of Kaposi-Juliusberg eruption and impetiginization, lisinopril was discontinued. Rapid involution of the skin lesions, was observed. Since, only minor skin lesions still persisted after 6 months of follow-up and treatment, the diagnosis of druginduced pemphigus foliaceus was established. It usually takes 1 - 6 months for angiotensin-converting enzyme inhibitors to induce pemphigus. All drugs taken by the patient, including homeopathic agents, over-the-counter drugs, and even medications that were discontinued should be taken into consideration. Medical history taking should be repeated in cases where there is no response to therapy. Sažetak Uvod: Lekovi se sve češće navode kao uzročnici pemfigusa. Lizinopril je inhibitor angiotenzinkonvertujućeg enzima (ACE - eng. angiotensinconverting enzyme) koji se koristi u lečenju hipertenzije, kongestivne srčane bolesti kao i u prevenciji renalnih i retinalnih komplikacija u dijabetesu melitus. Do sada su opisane različite reakcije na lek, ali samo jedan slučaj pemphigusa foliaceus (PF). Prikazujemo drugi slučaj u svetu PF indukovanog lizinoprilom komplikovanog Kaposi-Juliusbergovom variceliformnom erupcijim kod pacijenta sa diabetesom mellitus tip 2. Patofiziologija: PF je autoimuno bulozno oboljenje gde autoantitela klase IgG pogađaju intercelularni glikoprotein desmoglein-1. Do vezivanja ovih antitela koja pripadaju IgG4 potklasi, dolazi uglavnom u granuloznom sloju epidermisa nakon čega nastupa akantoliza, supkornealno i intraepidermalno formiranje bula. Novonastale bule karakteriše fragilnost; postavljene su superficijalno te lako ruptuiraju pri čemu ostavljaju erozije. Različiti faktori mogu uzrokovati pemfigus, a etiologija bolesti se najbolje opisuje kroz akronim PEMPHIGUS: PEsticidi, Malignitet, P tj. Farmacija, Hormoni, Infekcije i Imunizacije, Gastronomija, Ultravioletno zračenje i Stres. Lizinopril (C21H35N3O7) je lizinski derivat enalaprilata, aktivnog metabolita enalaprila. Sadrži amidnu grupu. Različiti neželjeni efekti na lizinopril su do sada opisani, ali samo jedan slučaj PF. Prikaz slučaja: Muškarac, star 60 godina iz okoline Trstenika primljen je sa supfebrilnim temperaturama. Brojne diseminovane umbilikovane vezikule i eritem bili su prisutni na koži lica, trupa i ekstremiteta, a semi-anularne erozije na koži trupa. Jasno ograničeni žućkasto-crvenkasti plakovi, mestimično grupisani, veličine do 2 cm, bili su lokalizovani na zadnjoj strani trupa (paravertebralno i vertebralno). Osim pojačanih injekcija na obe konjunktive, na ostalim vidljivim sluznicama nisu uočene patološke promene. Iz anamnestičkih podataka saznalo se da boluje od dijabetesa melitus tip 2 ukupno 10 godina, a od hipertenzije 2 godine, i da je od lekova redovno uzimao metformin i lizinopril. U porodičnoj anamnezi naveo je da su oba roditelja imala povišen pritisak, dok je majka bolovala od dijabetesa melitus i astme. Od 2007. godine kada su se pojavile prve promene na koži, lečen je pod dijagnozom atopijski dermatitis i to uglavnom lokalno. Međutim, pogoršanje kožnog stanja nastupilo je 1,5 mesec pre prijema na našu kliniku, kada je zbog febrilnosti, upućen prvo u regionalnu bolnicu gde je pod dijagnozom eritrodermije lečen pored lokalne terapije i sistemski kortikosteroidima, antihistaminicima i antibioticima. Histologija koja je rađena tom prilikom, upućivala je na eksfolijativni dermatitis kao reakciju na lek. Nakon 5 dana, došlo je do pogoršanja opšteg stanja pacijenta, febrilnosti, sa erupcijom novih kožnih lezija po tipu papulovezikulozne erupcije, te je premešten na Kliniku za dermatovenerologiju KCS u Beogradu. Po prijemu, uočene su semianularne erozije sa ostacima krovova bula kao i pojedinačni žućkasto-crvenkasti plakovi do 2 cm u prečniku na trupu i ekstremitetima, i brojne, diseminovane umbilikovane vezikule. Laboratorijske analize su ukazale na postojanje blage hiposideremijske anemije, i povišen IgE titar od 725 IU/ml (normalne vrednosti do 100). Imunološke analize su bile uredne, dok je virusološkim analizama zapažen četvorostruki pad titra HSV-1 tokom boravka u bolnici. Direktna, indirektna imunofluorescencija kao i histologija bile su kompatibilne sa PF. Lečenje: Nakon primene aciklovir tableta, antibiotika prema antibiogramu i metformina (kojeg je pacijent redovno uzimao) kao i insulina (nezadovoljavajuća glikoregulacija), uključen je prednisolon 40 mg/ dan kao i azatioprin 150 mg/dan, antiseptičke boje i kombinovane antibiotsko-kortikosteroidne kreme. Nakon 2 nedelje i rezolucije prvobitnih promena, uočene su nove − superficijelne bule kao i eritematozni, jasno ograničeni plakovi na licu, trupu i ekstremitetima. Histologija sa plakova potvrdila je nalaz PF moguće indukovanog lekovima. Na osnovu ponovljenih anamnestičkih podataka uočeno je da je do pogoršanja promena na koži došlo 6 meseci pošto je u terapiju uveden lizinopril. Lek je isključen, nakon čega je nastupilo rapidno poboljšanje: nestajanje plakova, epitelizacija erozija i prestanak javljanja novih bula. Nakon 6 meseci praćenja, utvrđeno je da na koži i dalje postoje retke, minimalno infiltrovane promene na trupu i ekstremitetima. Na osnovu svega iznetog, postavljena je dijagnoza PF pokrenutog lizinoprilom kod pacijenta sa dijabetesom melitus i Kaposi-Juliusbergovom variceliformnom reakcijom. Diskusija: Sledeći ACE inhibitori mogu indukovati PF (publikovani radovi): kaptopril, enalapril, lizinopril, fosinopril. Zbog tiol grupe (SH) kaptopril često uzrokuje neželjene reakcije na koži. Predloženi su različiti modeli kojim ACE inhibitori mogu oštetiti kožu, kako in vivo, tako i in vitro. Lizinopril je treći ACE inhibitor koji je devedesetih godina prošlog veka uveden u terapiju, nakon kaptoprila i enalaprila. Poznato je da su ACE inhibitori moćni induktori akantolize in vivo i in vitro. Do 17.9. 2012. godine ukupno 82 414 pacijenata imalo je neželjene reakcije na pomenuti lek. Među njima 35 (0,04%) je imalo pemfigoid, dok je 11 (0,01%) imalo pemfigus. Jedan od prijavljenih slučajeva pemfigusa je i naš pacijent. Većina navedenih pacijenata bila je starija od 60 godina. Do promena buloznog pemfigoida dolaziloje nakon 6−12 meseci a pemfigusa 1-6 meseci od uvođenja lizinoprila u terapiju. Cirkulišuća i za epidermis vezana antitela protiv dezmogleina 1 i dezmogleina 3, koja su prisutna kod pacijenata sa spontanim pemfigusom foliaceus odnosno vulgarnim pemfigusom, mogu se dokazati i kod pacijenata sa lekovima izazvanim pemfigusom kao što je to slučaj kod našeg pacijenta. Ipak, treba znati da prema podacima iz literature, kod pacijenata sa pemfigusom izazvanim penicilaminom (najčešće inkriminisani lek), direktni imunofluorescenti test ostaje negativan kod 10% a indirektni kod 30% obolelih. Posle 6 meseci od ukidanja lizinoprila, naš pacijent je idalje imao retke, minimalno infiltorovane male plakove (dijametra nekoliko mm) na trupu i ekstremitetima. Titar antidezmogleinskih antitela bio je nizak i iznosio je 1 : 20. Poznato je da se samo kod približno 40−50% pacijenata sa pemfigusom izazvanim lekovima koji poseduju tiol (SH) grupu bolest spontano povlači posle ukidanja inkriminisanog leka. Kada su u pitanju ostali lekovi, ovaj procenat nije viši od 15%. Zaključak: Kod svakog de novo slučaja pemfigusa, mora se isključiti uloga leka kao potencijalnog pokretača odnosno uzroka bolesti, s obzirom da svi lekovi koje je pacijent uzimao uključujući i vitamine i homeopatske lekove, pa čak i lekove koje je pacijent prestao da uzima, mogu biti pokretači bolesti. Kod svih pacijenata kod kojih ne dolazi do očekivanog terapijskog odgovora na primenjenu terapiju, treba ponovo insistirati na detaljnim anamnestičkim podacima.