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REVISTA DERMATOLÓGICA NOVIEMBRE 2003-2024, PIMECROLIMUS
(ELIDEL)
En este bloque de noticias destaca LA PSORIASIS (6,7,8,9), enfermedad eritematoescamosa ancestral y de difícil tratamiento. En la década de los 80 y hasta mediados de la década de los 90 No hubo grandes adelantos en el tratamiento de esta enfermedad, más allá de las fórmulas magistrales, preparadas con ácido salicílico, alquitrán de hulla, urea, esteroides tópicos, y la llamada PUVA terapia: el uso de PSORALENOS, combinado con radiación (Lámparas ultravioleta de espectro A). De allí el nombre P=PSORALENOS y UVA=ULTRAVIOLETA A.
CRONOLOGÍA DE LOS AVANCES EN EL TRATAMIENTOS DE LA PSORIASIS:
A.- TRATAMIENTOS: DÉCADA DEL 93-2003.
1.) En el año 1993 fue aprobado el CALCIPOTRIOL medicamento de uso tópico, con el nombre de DAIVONEX, al cual se le agregó posteriormente BETAMETASONA y sale al mercado con el nombre de DAIVOBET hecho que ocurre en el año 2003, ambos del laboratorio LEO Pharma.
2.) En el año 1997, la FDA aprueba el TAZAROTENO derivado de la vitamina A, PARA EL TRATAMIENTO DE LA psoriasis, acné juvenil y el fotoenvejecimiento.
Desarrollado por los laboratorios ALLERGAN Pharmaceuticals, BIOGEN y GLENMARK Pharmaceuticals, con varios nombres: TAZORAC, AVAGE, ZORAC, TAZRET y otros.
3.) En el año 1998 LA FDA aprueba un nuevo medicamento denominado ETANERCEPT, desarrollado por el laboratorio IMMUNEX y luego adquirido por el laboratorio AMGEN, con el nombre de ENBREL, para el tratamiento de la PSORIASIS (EN PLACA y ARTRÍTICA), también para la ESPONDILITIS ANQUILOSANTE, ARTRITIS JUVENIL y ARTRITIS REUMATOIDE.
Este medicamentos es una PROTEÍNA cuyo mecanismo de acción es una INHIBICIÓN DEL FACTOR DE NECROSIS TUMORAL ALFA ((TNF-α), disminuyendo la inflamación y el dolor. En el caso de la PSORIASIS las placas y síntomas desaparecen.
Este medicamento FUE EL QUE DIO el gran paso hacia una GRAN MEJORÍA DE LOS PACIENTES CON PSORIASIS, en VENEZUELA y en el mundo, era "administrado GRATUITAMENTE en el IVSS (Seguridad Social), hasta que llegó la gran crisis a mediados de la década de los 2000.
4.) Para el año 2002 la FDA aprueba el medicamento ADALIMUMAB, del laboratorio AbbVie, conocido con el nombre de HUMIRA, un producto biológico, ANTICUERPO MONOCLONAL inmunoglobulinico (IG 1), que también inhibe al igual que el ETANERCEPT el factor de necrosis tumoral ALFA (TNF-α).
El ADALIMUMAB se utiliza en: ARTRITIS REUMATOIDE JUVENIL, ESPONDILITIS ANQUILOSANTE, PSORIASIS EN PLACAS, ENFERMEDAD DE CROHN, UVEÍTIS NO INFECCIOSA, ARTRITIS PSORIÁSICA, ARTRITIS IDIOPÁTICA JUVENIL POLIARTICULAR. HIDRADENITIS SUPURATIVA y COLITIS ULCEROSA.
También administrado "gratuitamente"en venezuela en los institutos de seguridad Social (IVSS) hasta mediados de la década del 2000.
5.) En el año 2003 la FDA aprueba el ALEFACEPT, desarrollado por el laboratorio BIOGEN, con el nombre comercial de AMEVIVE, actúa como inmunomodulador disminuyendo la actividad de los linfocitos T, y con ello el estado inflamatorio propio de la psoriasis. La presentación es en viales con polvo para suspensión de 15 mg, para uso intramuscular.
6.) Ese mismo año del 2003 la FDA aprueba el medicamento EFALIZUMAB, con el nombre comercial de RAPTIVA, del mismo laboratorio BIOGEN. Anticuerpo monoclonal con efecto inmunosupresor, inhibiendo la respuesta inflamatoria en los pacientes con psoriasis. En el año 2009 fue retirado del mercado debido a efectos secundarios severos.
B.-NUEVOS TRATAMIENTOS PARA LA PSORIASIS: DÉCADA 2014-2024.
A partir de la década de los 2010, aparecieron en el mercado los siguientes medicamentos para el tratamiento de la PSORIASIS, en orden cronológico:
1.) SECUKINUMAB: Este medicamento es otro anticuerpo monoclonal, el cual actúa inhibiendo la interleuquina 17A (IL-17A), la cual se ha descubierto que es clave en el proceso inflamatorio que produce la psoriasis.
Desarrollado por el laboratorio NOVARTIS y aprobado por al FDA el 12 de Diciembre de 2014. La EMA (comisión Europea), también lo aprobó en enero del 2015. Nombre comercial COSENTYX. Su uso es fundamentalmente en pacientes adultos con psoriasis en placa moderada a grave candidatos a tratamiento sistémico o fototerapia. Presentación en solución para ser inyectado vía subcutanea.
2.) IXEKIZUMAB: También un anticuerpo monoclonal similar al SECUKINUMAB, porque actúa bloqueando la interleuquina-17A (IL-17A), aprobado por la FDA el 28 de marzo del 2017, con el nombre comercial de TALTZ.
Desarrollado por el laboratorio ELI LILLY; también utilizado en psoriasis en placa moderada a severa. Presentación: Jeringas precargadas de 80 Mg en 1 ml de solución, para administración vía subcutánea.
3.) TILDRAKIZUMAB: Otro anticuerpo MONOCLONAL, que en este caso a diferencia del anterior, inhibe la interleuquina-23 (IL-23), el cual ha probado mejorar en un 50% las lesiones de psoriasis, disminuyendo la inflamación cutánea.
Desarrollado por el laboratorio ALMIRALL S.A. con el nombre comercial de ILUMETRI. Aprobado por la FDA el 27 de Marzo del 2018 para el tratamiento de la psoriasis en placa en adultos, moderada o grave. La presentación es en solución para inyectar vía subcutanea.
4.) DEUCRAVACITINIB: Este medicamento fue aprobado por la FDA en el año 2022 y también aprobado por la EMA (Agencia Europea de Medicamentos), cuyo mecanismo de acción es inhibir la tirosinasa-2 (TYK2), logrando con estos disminuir la inflamación y formación de placas cutáneas.
Desarrollado por el laboratorio Bristol Myer Squibb con el nombre comercial de SOTYKTU. Su administración es vía oral en comprimidos de 6 Mg para ser administrado 1 vez al día en casos de psoriasis en placa de moderada a grave, convirtiéndose en el primer medicamento de uso oral para tratar esta patología.
En VENEZUELA hoy dia DICIEMBRE 2024 no se consigue DAIVOBET, ni ENBREL , TAMPOCO HUMIRA. Al ser costosos estos medicamentos, NO TODOS LOS PACIENTES PUEDEN ADQUIRIRLOS Y para ello deben traerlos del exterior. Tampoco se consiguen LOS nuevos MEDICAMENTOS desarrollados a partir de la década de los 2010.
Otros temas de interés en esta publicación: VITILIGO (1,2,3), PÉNFIGO VULGAR y DAPSONA (4), PITIRIASIS LIQUENOIDE (5), ABSCESO HEPÁTICO (10).
Saludos,,,
Dr. José Lapenta.
ENGLISH
This news block highlights PSORIASIS (6,7,8,9), an ancestral erythematous-squamous disease that is difficult to treat. In the 80s and until the mid-90s there were no major advances in the treatment of this disease, beyond the master formulas, prepared with salicylic acid, coal tar, urea, topical steroids, and the so-called PUVA therapy: the use of PSORALENS, combined with radiation (ultraviolet A spectrum lamps). Hence the name P=PSORALENS and UVA=ULTRAVIOLET A.
CHRONOLOGY OF ADVANCES IN THE TREATMENT OF PSORIASIS:
A.- TREATMENTS: DECADE OF 93-2003.
1.) In 1993, CALCIPOTRIOL, a topical drug, was approved under the name DAIVONEX, to which BETAMETHASONE was later added and it was launched on the market under the name DAIVOBET, which occurred in 2003, both from the LEO Pharma laboratory.
2.) In 1997, the FDA approved TAZAROTENE, a vitamin A derivative, FOR THE TREATMENT OF psoriasis, juvenile acne and photoaging.
Developed by ALLERGAN Pharmaceuticals, BIOGEN and GLENMARK Pharmaceuticals laboratories, under various names: TAZORAC, AVAGE, ZORAC, TAZRET and others.
3.) In 1998, the FDA approved a new drug called ETANERCEPT, developed by the IMMUNEX laboratory and later acquired by the AMGEN laboratory, under the name ENBREL, for the treatment of PSORIASIS (PLAQUE and ARTHRITIC), also for ANKYLOSING SPONDYLITIS, JUVENILE ARTHRITIS and RHEUMATOID ARTHRITIS.
This medication is a PROTEIN whose mechanism of action is an INHIBITION OF THE TUMOUR NECROSIS FACTOR ALPHA ((TNF-α), decreasing inflammation and pain. In the case of PSORIASIS, plaques and symptoms disappear.
This medication WAS THE ONE THAT GAVE the great step towards a GREAT IMPROVEMENT OF PATIENTS WITH PSORIASIS, in VENEZUELA and in the world, it was "administered FREE in the IVSS (Social Security), until the great crisis came in the mid-2000s.
4.) In 2002, the FDA approved the medication ADALIMUMAB, from the AbbVie laboratory, known by the name of HUMIRA, a biological product, immunoglobulin MONOCLONAL ANTIBODY (IG 1), which also inhibits the tumour necrosis factor ALPHA (TNF-α) like ETANERCEPT.
The ADALIMUMAB is used in: JUVENILE RHEUMATOID ARTHRITIS, ANKYLOSING SPONDYLITIS, PLAQUE PSORIASIS, CROHN'S DISEASE, NON-INFECTIOUS UVEITIS, PSORIATIC ARTHRITIS, POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS. HIDRADENITIS SUPPURATIVA and ULCERATIVE COLITIS.
It was also administered "free of charge" in Venezuela in the Social Security Institutions (IVSS) until the mid-2000s.
5.) In 2003, the FDA approved ALEFACEPT, developed by the BIOGEN laboratory, with the commercial name AMEVIVE, which acts as an immunomodulator by decreasing the activity of T lymphocytes, and thus the inflammatory state of psoriasis. It is presented in vials with 15 mg powder for suspension, for intramuscular use.
6.) That same year, 2003, the FDA approved the drug EFALIZUMAB, with the trade name RAPTIVA, from the same laboratory BIOGEN. It is a monoclonal antibody with an immunosuppressive effect, inhibiting the inflammatory response in patients with psoriasis. In 2009, it was withdrawn from the market due to severe side effects.
B.- NEW TREATMENTS FOR PSORIASIS: DECADE 2014-2024.
Beginning in the 2010s, the following drugs for the treatment of PSORIASIS appeared on the market, in chronological order:
1.) SECUKINUMAB: This drug is another monoclonal antibody, which acts by inhibiting interleukin 17A (IL-17A), which has been discovered to be key in the inflammatory process that causes psoriasis.
Developed by the NOVARTIS laboratory and approved by the FDA on December 12, 2014. The EMA (European Commission) also approved it in January 2015. Trade name COSENTYX. Its use is primarily in adult patients with moderate to severe plaque psoriasis who are candidates for systemic treatment or phototherapy. Presentation in solution to be injected subcutaneously.
2.) IXEKIZUMAB: Also a monoclonal antibody similar to SECUKINUMAB, because it acts by blocking interleukin-17A (IL-17A), approved by the FDA on March 28, 2017, with the trade name TALTZ.
Developed by the ELI LILLY laboratory; also used in moderate to severe plaque psoriasis. Presentation: Pre-filled syringes of 80 mg in 1 ml of solution, for subcutaneous administration.
3.) TILDRAKIZUMAB: Another MONOCLONAL antibody, which in this case unlike the previous one, inhibits interleukin-23 (IL-23), which has been proven to improve psoriasis lesions by 50%, reducing skin inflammation.
Developed by the laboratory ALMIRALL S.A. with the trade name ILUMETRI. Approved by the FDA on March 27, 2018 for the treatment of plaque psoriasis in adults, moderate or severe. It is presented in a solution for subcutaneous injection.
4.) DEUCRAVACITINIB: This drug was approved by the FDA in 2022 and also approved by the EMA (European Medicines Agency), whose mechanism of action is to inhibit tyrosinase-2 (TYK2), thereby reducing inflammation and the formation of skin plaques.
Developed by the Bristol Myer Squibb laboratory under the trade name SOTYKTU. It is administered orally in 6 mg tablets to be administered once a day in cases of moderate to severe plaque psoriasis, becoming the first oral medication to treat this pathology.
In VENEZUELA today DECEMBER 2024, DAIVOBET, ENBREL, NOR HUMIRA are available. Since these medications are expensive, NOT ALL PATIENTS CAN ACQUIRE THEM and must bring them from other countries. New drugs developed since the 2010s are also not available.
Other topics of interest in this publication: VITILIGO (1,2,3), PEMPHIGUS VULGARIS and DAPSONE (4), PITYRIASIS LICHENOIDES (5), LIVER ABSCESS (10).
Greetings,,,
Dr. José Lapenta.
PSORIASIS, PIMECROLIMUS (ELIDEL), TADALAFIL (CIALIS), SILDENAFIL (VIAGRA), VARDENAFIL (LEVITRA), VITILIGO.
2.) Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo.
4.) Childhood pemphigus vulgaris treated with dapsone: a case report.
5.) Infectious causes of pityriasis lichenoides: a case of fulminant infectious mononucleosis.
6.) Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial.
7.) A randomized trial of etanercept as monotherapy for psoriasis.
10.) Recent Changes of Organism and Treatment in Pyogenic Liver Abscess].
1.) Expansion of vitiligo lesions is associated with
reduced epidermal CDw60 expression and increased expression of
HLA-DR in perilesional skin.
Br J Dermatol. 2003 Oct;149(4):739-48.
Le Poole IC, Stennett LS, Bonish BK, Dee L, Robinson JK, Hernandez
C, Hann SK, Nickoloff BJ.
Department of Pathology, Cardinal Bernardin Cancer Center Rm 203,
Loyola University, 2160 South First Avenue, Maywood, Chicago, IL
60153, U.S.A. ilepool@lumc.edu
BACKGROUND: Detection of CDw60 in skin is representative of
ganglioside D3 expression. This ganglioside is expressed primarily
by melanocytes, and is of interest as a membrane antigen targeted
by immunotherapy for melanoma patients. Expression of CDw60 by
keratinocytes is defined by the presence of T-helper cell (Th)1
vs. Th2 cytokines, and can serve as a sentinel molecule to
characterize an ongoing skin immune response. OBJECTIVES: These
immunobiological characteristics have provided the incentive to
study the expression of CDw60 in the context of progressive
vitiligo. METHODS: Frozen sections were obtained from control skin
and from vitiligo lesions and immunostained to show CDw60. Cells
were cultured, their CDw60 expression studied and ribonuclease
protection assays run to detect cytokine mRNA. RESULTS: Resistance
to cytokine-mediated regulation of CDw60 expression was
demonstrated in vitro by melanocytes, which appeared capable of
generating autocrine and paracrine regulatory molecules supporting
CDw60 expression. Induction of CDw60 expression was inhibited by
antibodies to interleukin (IL)-4, suggesting that this cytokine
was responsible, at least in part, for melanocyte-induced CDw60
expression. Marginal skin from patients with progressive
generalized vitiligo consistently showed a reduction in epidermal
CDw60 expression alongside elevated human leucocyte associated
antigen (HLA)-DR expression at the margin. It thus appears that
inflammatory infiltrates present in marginal skin generate type 1
rather than type 2 cytokines, supportive of a cell-mediated
autoimmune response. CONCLUSIONS: These results support an active
role of melanocytes within the skin immune system, and associate
their loss in generalized vitiligo with a cell-mediated immune
response mediated by type 1 cytokines.
2.) Erbium:YAG laser and cultured epidermis in the surgical
therapy of stable vitiligo.
Arch Dermatol. 2003 Oct;139(10):1303-10.
Guerra L, Primavera G, Raskovic D, Pellegrini G, Golisano O, Bondanza S, Paterna P, Sonego G, Gobello T, Atzori F, Piazza P, Luci A, De Luca M.
Laboratory of Tissue Engineering, Istituto Dermopatico dell'Immacolata, Rome, Italy.
OBJECTIVE: To induce complete and reproducible repigmentation of large "stable" vitiligo lesions by means of autologous cultured epidermal grafts using a rapid, simple, and minimally invasive surgical procedure. DESIGN: Achromic epidermis was removed by means of appropriately settled erbium:YAG laser, and autologous epidermal grafts were applied onto the recipient bed. Melanocyte content was evaluated by dopa reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. SETTING: A biosafety level 3-type cell culture facility, a surgical ambulatory department, and a dermatological department in a hospital. PATIENTS: Twenty-one patients with different types of vitiligo were admitted to the study and treated with autologous cultured epidermal grafts. Inclusion criteria were failure of at least 2 standard medical approaches; no therapy for at least 12 months; no progression of old lesions or appearance of new lesions; no Koebner phenomenon within the past 18 months; and no autoimmune disorders. RESULTS: The average percentage of repigmentation in 21 patients was 75.9% (1759.7 cm2 repigmented/2315.8 cm2 transplanted). Three patients showed a reactivation of their vitiligo and did not show repigmentation. The remaining 18 patients, with 43 distinct lesions, showed an average percentage of repigmentation of 90% (1759.7 cm2 repigmented/1953.4 cm2 transplanted). CONCLUSIONS: Under appropriate conditions, cultured epidermal grafts induce complete repigmentation of stable vitiligo lesions. Erbium:YAG laser surgery can supply a fast and precise tool for deepithelialization, hence allowing treatment of large vitiligo lesions during a single surgical operation.
3.) Open trial of topical tacalcitol [1 alpha 24(OH)2D3]
and solar irradiation for vitiligo vulgaris: upregulation of
c-Kit mRNA by cultured melanocytes.
Eur J Dermatol. 2003 Jul-Aug;13(4):372-6.
Katayama I, Ashida M, Maeda A, Eishi K, Murota H, Bae SJ.
Department of Dermatology, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki, Japan. nkatayam@net.nagasaki-u.ac.jp
Vitiligo vulgaris is a common skin disease, however some cases show poor clinical responses to topical steroid ointment or PUVA therapy. Such regimens are generally avoided in the treatment of facial lesions or in pediatric cases because of the undesirable side effects. To confirm the excellent response to combination therapy with topical vitamin D3 ointment and solar irradiation for vitiligo achieved in the initial patients, we conducted an open trial on other patients, most of whom had poor clinical responses to the prior therapies. Fifteen patients (9 men and 6 women) with vitiligo vulgaris were enrolled in this study. Each patient was instructed to sunbathe for 30 minutes within 1 hour after topical application of the tacalcitol [1 alpha 24(OH)(2)D(3)] ointment or cream to the skin lesions every day. Six of 15 patients showed a fair and excellent clinical response to the combination therapy (more than 30% clearance of the vitiligo). The clinical effect was more apparent in patients with a history of less than 5 years of vitiligo (4 of 6 cases) in contrast to those with a history of more than 5 years (2 of 9 cases). In vitro experiments revealed that tacalcitol upregulated the expression of c-Kit mRNA by melanocytes irradiated with linear polarized infrared, UVA or short period solar irradiation. These results suggest that combination therapy with topical vitamin D(3) ointment and solar irradiation can be used as an alternate therapy for vitiligo vulgaris.
4.) Childhood pemphigus vulgaris treated with dapsone: a case
report.
Pediatr Dermatol. 1998 Sep-Oct;15(5):381-3.
Bjarnason B, Skoglund C, Flosadottir E.
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
A 5-year-old boy developed hemorrhagic mucocutaneous blisters on various parts of the body leading to fetor, dysphagia, dysuria, anal pruritus, pain on defecation, and weight loss. The histopathology showed the classic features of pemphigus vulgaris, and direct immunofluorescence showed intercellular deposition of IgG and C3 in the epidermis. Circulating pemphigus antibodies were also detected. He was treated with a combination of systemic prednisone and dapsone which induced a rapid remission and controlled the disease well. He has been in remission for 1 year and 7 months with no immunosuppressive therapy except for the use of topical agents for the oral lesions. An adjuvant to corticosteroids has been used only once before in children with pemphigus vulgaris under the age of 12 years. This is the third and the youngest child in the literature treated in this fashion.
5.) Infectious causes of pityriasis lichenoides: a case of fulminant infectious
J Am Acad Dermatol. 2003 Aug;49(2 Suppl Case Reports):S151-3.
Klein PA, Jones EC, Nelson JL, Clark RA.
Department of Dermatology, School of Medicine, HSC T-16, Room 060,
State University of New York at Stony Brook, Stony Brook, NY
11794-8165, USA. PKLEIN00@yahoo.com
Pityriasis lichenoides is a rare cutaneous eruption of unknown
cause that spans a spectrum of clinical severity. Infectious
agents have long been suspected as etiologic factors. The present
case is the first to demonstrate a known EBV-mediated process
evolving and resolving in concert with pityriasis lichenoides.
Epstein-Barr virus, Toxoplasma gondii, and HIV are the most
frequently reported infectious triggers of pityriasis lichenoides.
Pityriasis lichenoides may arise secondary to EBV-mediated acute
infectious mononucleosis.
6.) Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial.
JAMA. 2003 Dec 17;290(23):3073-80.Comment in:
JAMA. 2003 Dec 17;290(23):3133-5.
Gordon KB, Papp KA, Hamilton TK, Walicke PA, Dummer W, Li N, Bresnahan BW, Menter A; Efalizumab Study Group.
Loyola University Medical Center, Maywood, Ill 60153, USA. kgordon@lumc.edu
CONTEXT: Because T-cell interactions are involved in the pathophysiology of psoriasis, therapy with a T-cell modulator may have beneficial effects on psoriasis severity and health-related quality of life (HRQL). OBJECTIVE: To assess the efficacy and safety of efalizumab, a T-cell modulator, in patients with plaque psoriasis. DESIGN, SETTING, AND PATIENTS: Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial involving 556 adult patients with stable, moderate to severe plaque psoriasis and conducted at 30 study centers in the United States and Canada between January and July 2002. INTERVENTIONS: Patients were randomly assigned in a 2:1 ratio to receive 12 weekly doses of subcutaneous efalizumab, 1 mg/kg (n = 369), or placebo equivalent (n = 187). MAIN OUTCOME MEASURES: At least 75% improvement on the Psoriasis Area and Severity Index (PASI-75); improvement on the overall Dermatology Life Quality Index (DLQI), Itching Visual Analog Scale (VAS), and Psoriasis Symptom Assessment (PSA) at week 12 vs baseline. RESULTS: Efalizumab-treated patients experienced significantly greater improvement on all end points than placebo-treated patients. Twenty-seven percent of efalizumab-treated patients achieved PASI-75 vs 4% of the placebo group ( P<.001). Efalizumab-treated patients exhibited significantly greater mean percentage improvement than placebo-treated patients on the overall DLQI (47% vs 14%; P<.001), Itching VAS (38% vs -0.2%; P<.001), and PSA frequency and severity subscales (48% vs 18% and 47% vs 17%, respectively; P<.001 for both) at the first assessment point. Efalizumab was safe and well tolerated, with primarily mild to moderate adverse events. CONCLUSION: In this 12-week study, efalizumab resulted in significant improvements in clinical end points, including physician-assessed and dermatology-specific patient-reported HRQL measures, in patients with moderate to severe plaque psoriasis.
7.) A randomized trial of etanercept as monotherapy for
psoriasis.
Arch Dermatol. 2003 Dec;139(12):1627-32; discussion 1632.
Gottlieb AB, Matheson RT, Lowe N, Krueger GG, Kang S, Goffe BS,
Gaspari AA, Ling M, Weinstein GD, Nayak A, Gordon KB, Zitnik
R.
Clinical Research Center, University of Medicine and Dentistry
of New Jersey-Robert Wood Johnson Medical School, New Brunswick,
08901-0019, USA. gottliab@umdnj.edu
OBJECTIVE: To determine safety and efficacy of monotherapy with
etanercept. DESIGN: Randomized, double-blind,
placebo-controlled, multicenter study. SETTING: Outpatient,
ambulatory; private practice and university dermatology research
centers. PATIENTS: Patients aged at least 18 years, with plaque
psoriasis involving 10% or more of body surface area; 148 were
screened and 112 were randomly assigned to treatment groups and
received study drug. INTERVENTIONS: Patients received placebo or
etanercept, 25 mg, subcutaneously twice a week for 24 weeks.
Other psoriasis therapies were limited during the study. MAIN
OUTCOME MEASURES: Safety measurements included tracking of
adverse events and laboratory values. Efficacy was evaluated
using the Psoriasis Area and Severity Index (PASI); the primary
end point was a 75% improvement in PASI. Other efficacy
measurements included patient and physician global assessments
and quality-of-life measures. RESULTS: After 12 weeks of
treatment, 17 (30%) of the 57 etanercept-treated patients and 1
(2%) of the 55 placebo-treated patients had achieved PASI 75%,
and after 24 weeks, 32 (56%) of etanercept-treated patients and
3 (5%) of placebo-treated patients had reached this level
(P<.001 for both time points). By 24 weeks, psoriasis was
clear or minimal by physician's global assessment in more than
50% of patients who received etanercept. Treatment failure (PASI
response <50) occurred in 23% of patients at week 24. All
other measures confirmed the efficacy of etanercept. Adverse
events were similar among etanercept and placebo groups.
CONCLUSION: Etanercept monotherapy provided significant benefit
to patients with psoriasis and had a favorable safety
profile.
8.) Treatment of psoriasis with alefacept: correlation of clinical improvement with reductions of memory
Arch Dermatol. 2003 Dec;139(12):1563-70.
Gordon KB, Vaishnaw AK, O'Gorman J, Haney J, Menter A;
Alefacept Clinical Study Group.
Department of Medicine, Division of Dermatology, Loyola
University Medical Center, Maywood, IL 60153, USA.
kgordon@lumc.edu
OBJECTIVE: To examine the relationship between the
pharmacodynamic and antipsoriatic effects of alefacept, a
biologic agent that targets CD4+ and CD8+ memory T cells.
DESIGN: Randomized, double-blind, placebo-controlled study of
3 parallel groups. SETTING: Fifty-one study centers. PATIENTS:
Five hundred fifty-three patients with chronic plaque
psoriasis. INTERVENTIONS: Patients were randomized (1:1:1) to
1 of the following 3 cohorts: alefacept, 7.5 mg, in both
courses (cohort 1); alefacept, 7.5 mg, in the first course and
placebo in the second course (cohort 2); or placebo in the
first course and alefacept, 7.5 mg, in the second course
(cohort 3). In each course, alefacept or placebo was
administered by intravenous bolus once weekly for 12 weeks,
followed by 12 weeks of observation. MAIN OUTCOME MEASURES:
Circulating lymphocyte levels and the Psoriasis Area Severity
Index. RESULTS: One or 2 courses of alefacept reduced CD4+ and
CD8+ memory T-cell counts, while sparing the naive population.
At 12 weeks after the last dose of alefacept in courses 1 and
2, 88% and 83% of patients, respectively, had CD4+ cell counts
greater than the lower limit of normal. In course 1,
alefacept-treated patients with the largest decreases in
memory T-cell counts experienced the greatest reductions in
disease activity (P<.001). The duration of clinical benefit
seemed to be longer among patients who had the greatest
reduction in CD4+ and CD8+ memory T-cell counts. CONCLUSIONS:
One or 2 courses of intravenous alefacept reduced circulating
memory T-cell counts while sparing the naive T-cell
population. The reductions in memory T-cell counts were
related to all measures of disease activity evaluated and the
duration of response to therapy, suggesting that prolonged
remissions of psoriasis can be attained with reduction of the
pathogenic T-cell count.
9.) Possible role of Malassezia furfur in psoriasis: modulation of TGF-beta1, integrin, and HSP70 expression in human keratinocytes and in the skin of psoriasis-affected patients.
J Cutan Pathol. 2004 Jan;31(1):35-42.
Baroni A, Paoletti I, Ruocco E, Agozzino M, Tufano MA, Donnarumma G.
Department of Dermatology, and Department of Experimental Medicine: Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy.
BACKGROUND: Psoriasis is a disease characterized by an abnormal pattern of keratinocyte growth and differentiation. Malassezia furfur forms part of the normal human skin flora. It may also be involved in the pathogenesis of psoriasis. To define the role of M. furfur in the pathogenesis of psoriasis, we investigated how M. furfur regulates molecules involved in cell migration and proliferation. The experiments were performed using human keratinocytes and skin biopsies from M. furfur-positive and -negative psoriasis-affected patients. In addition, we examined the signal transduction mechanisms involved. MATERIALS AND METHODS: Western blot analysis was performed on human keratinocytes lysates treated or untreated with M. furfur and on biopsies from healthy and psoriasis patients. Signal transduction mechanisms involved were evaluated by electrophoretic mobility shift assay using the AP-1 inhibitor curcumin. RESULTS: We found that M. furfur up-regulates transforming growth factor-beta1 (TGF-beta1), integrin chain, and HSP70 expression in human keratinocytes via AP-1-dependent mechanism. In the biopsies of M. furfur-positive psoriasis-affected patients, an increase in TGF-beta1, integrin chains, and HSP70 expression was found. CONCLUSION: Our data suggest that M. furfur can induce the overproduction of molecules involved in cell migration and hyperproliferation, thereby favoring the exacerbation of psoriasis
10.) [Recent Changes of Organism and Treatment in Pyogenic
Liver Abscess]
.
Taehan Kan Hakhoe Chi. 2003 Dec;9(4):275-283.
[Article in Korean]
Nah BK, Kim YS, Moon HS, Park KO, Kim SM, Lee YS, Yang HW, Seo SW,
Kim SH, Lee BS, Kim NJ, Lee HY.
Department of Internal medicine, Chungnam National University
College of medicine, Daejeon, Korea.
leehy@hanbat.chungnam.ac.kr
BACKGROUND/AIMS: With the advance of antibiotics and the
development of newer imaging techniques, marked changes in
etiology, diagnosis, treatment and prognosis of liver abscess have
been reported. METHODS: We reviewed the clinical data related to
94 patients with pyogenic liver abscess. RESULTS: Of the 94
patients in the study group, the male to female ratio was 1.4:1
and the peak incidence of liver abcess was in the 7th decade.
About three quaters (74.5%) of the abcesses were of unknown
origin. The predominant location was in the right lobe (70.3%).
Single lesion was found in 80 patients and multiple lesions in 14
patients. Pathogens were identified in 67 patients, of which
Klebsiella pneumoniae (65.7%) and E. coli (16.4%) were the most
common. The modalities of treatment were percutaneous drainage
with antibiotics (73.4%), percutaneous aspiration with antibiotics
(16.0%), or antibiotics alone (8.5%). The case fatality rate,
mainly from associated underlying diseases, was 9 cases (9.6%).
Associated diseases were diabetes mellitus (14.9%) and malignancy
(10.6%). CONCLUSIONS: Our study revealed that the most common
organism was Klebsiella pneumoniae and percutaneous needle
aspiration and/or catheter drainage were safe and effective
treatment modalities for pyogenic liver abscess. Prognosis was
determined by the underlying condition.
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DATA-MÉDICOS/ DERMAGIC JOURNAL/DECEMBER 2.003-2024/ DR. JOSE
LAPENTA R.
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