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DICIEMBRE 2.003
DECEMBER 2.003
VITILIGO, PEMPHIGUS,
PITYRIASIS LICHENOIDES, PSORIASIS AND EFALIZUMAB, ETARNECEPT, ALEFACEPT,
MALASSEZIA FURFUR, PYOGENIC LIVER ABSCESS.
1.)
Expansion of vitiligo lesions is associated with reduced
epidermal CDw60 expression and increased expression of HLA-DR in perilesional
skin.
2.) Erbium:YAG laser and cultured epidermis in the surgical therapy of stable
vitiligo.
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.
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.
8.) Treatment of psoriasis with alefacept:
correlation of clinical improvement with reductions of memory T-cell counts.
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.
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. [email protected]
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 disepithelialization, 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. [email protected]
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.
[email protected]
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. [email protected]
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. [email protected]
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. [email protected]
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. [email protected]
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-MEDICOS/DERMAGIC-EXPRESS /DECEMBER JOURNAL 2.003/ DR. JOSE
LAPENTA R.
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