PITIRIASIS LIQUENOIDE CRÓNICA

Evandro Rivitti
Profesor Titular del Departamento de Dermatologla de la Facultad de Medicina de la Universidad de Sao Paulo

Será discutida la posición nosológica de la dolencia, sus características clínicas, histopatológicas y su terapéutica. Serán presentadas características de enfermedades en Sao Paulo, Brasil.

 

FOTOFERESIS: ESTUDIOS CLÍNICOS Y MECANISMOS

Richard L. Edelson, M.D.
Professor and Chairman Yale University School of Medicine

Photopheresis, a technique by wich expanded clones of pathogenic T cells are exposed ex vivo to photoactivated 8-methoxypsoralen and then returned intravenously to the afflicted patient, is now in use in more than 100 centers worldwide. It has been approved as a standard therapy for advanced cutaneous T cell lymphoma (CTCL) for the past seven years, and promising results have been reported in clinical trials in scleroderma, graftversus-host disease, rheumatoid arthritis, lupus erythematosus, AIDS, pemphigus and heart transplant rejection.

These clinical trials will be discussed in the context of recent information about the mechanism of action. Specifically, new information suggests that the treatment may substantially increase the amount of "empty" class I major histocompatibility molecules at the irradiated cell surface, while instantaneously releasing clone specific peptides into the medium. Data will be presented raising the possibility that these two effects, combined with exposure of the cells to subphysiologic temperature, may combine to make previously "invisible" surface antigens antigenic on reinfusion of the treated cells. The implications of these findings will be placed in the perspective of the clinical efficacy of the treatment.

 

GLUCOCORTICOIDE

Thomas J. Lawley, M.D.
Dean and Professor of Dermatology. Emory University School of Medicine.

 

Absortion/Distribution

• GCS absorbed in the jejunum > than 50% of prednisone absorbed.
• Food delays buj does not decrease absorption.
• Cortisol-binding globulin (CBG transcortin) is the primary endogenous carrier protein; free fraction represents the active form.
• CBG is a low-capacity, high-affinity binding reserve.
• Albumin is a high-capacity, low-affinity binding reserve.
• Synthetic GCS bind less avidly than endogenous cortisol.

 

Metabolism/Excretion

• 11-beta hydroxydehydrogenase (liver) is necessary to convert cortisone to hydrocortisone and prednisone to prednisolone.
• Liver desease may impair the conversion, and thus, prednisolone is appropiate for this patient population.
• Liver desease may result in decreased albumin.

 

Mechanism of action

Inmunologic Effects

• GCS have a greater effect of T lymphocytes than on B lymphocytes (thus little impairment on antibody synthesis).
• T lymphocytes are re-directed to reticuloendothelial system at sites distant from primary sites of inflammation.
• Monocyte function is altered.
• Macrophages unavailable for antigen processing.
• Langerhans cells have decreased surface markers and impaired antigen processing.

 

Mechanism of action

Inmunologic Effects

• Prevent inmunologically competent WBC subsets from reaching site of inflammation, total number cells unaffected.
• PMNs are increased in circulation through release of bone marrow reserves and decreased margination to endothelial cells.
• No change in PMN function.
• PMN count is typically 15 000-20 000/cu mm on moderate to high-dose GCS - therapy.

 

Mechanism of action

Inmunologic Effects

• Eosinophils and y basophils have GCS-induced decreased numbers, inhibited function and impaired recruitment.
• Mast cells have impaired release of histamine and kinins.
• GCS leads to decreased IL-1 and IL-2 production.
• Decreased gamma-interferon production.

 

Mechanism of action

Inmunologic Effects

• GCS-induced vascular effects.
• Vasoconstriction and decreased permeability of peripheral capillaries.
• Cells are unable to traverse the endothelial basement membrane to reach sites of inflammation.
• Decreased prostagladin, leukotriene, and hydroxycosatetranoic acid production and decreased participation in inflammatory processes.
• CGS inhibit lysosomal enzyme release in vitro.

 

Common Corticoesteroid Complications

• Obesity
• Striae
• Bruisability
• Growth disturbances
• Hypertension
• Moon facies
• Excessive appetite
• Decreased cell-mediated immunity
• Neutrophilia
• Lynphocytopenia
• Increased infections
• Delayed wound healing
• Increased excretion of sodium and potassium
• Carbohydrate intolerance
• Personality disturbances
• Posterior subcapsular cataracts

 

Musculoskeletal Effects

Aseptic Bone Necrosis

• Appearance as early as six weeks but usually 3-6 months of continuous GCS therapy.
• Prevailing therapy regarding mechanism involves microemboli of subchondral endoarterioles.
• Femur is the bone most commonly affected.

 

Osteoporosis

• Most bone loss occurs within first 3-12 months of steroid treatment, with slowing of bone loss in subsequent years.
• Greater risk in elderly postmenopausal women, particularly those who are immobilized and patients with RA.

Management:

• Calcium 1- 1,5 g/day
• Excercise
• Vitamin D supplement 50 000 units, 2-3 times a week.

 

Steroid Myopathy

• Due to decreased glucose and amino acid uptake by the muscles.
• More prevalent with steroids possessing a 9-alpha fluorine configuration (i.e., triamcinolone).
• No relationship to dosage or duration.
• Myopathy is proximal, symmetrical, and involves both upper and lower extremities.
• First complaint is usually inability to climb stairs.

 

Ophthalmologic Complications

• Posterior subcapsular cataracts are a common ocular side effect.
• Incidence between 11-30%, more frequent in children than adults.
• Patients with R.A. and who have taken steroids >1 year are more susceptible.
• Cataracts generally bilateral and asymptornatic until advanced.
• Alternate day therapy does not preclude their formation.
• Slit lamp exam recommended every 6-12 months for patient on long-term GCS.

 

Considerations in Pregnancy

• Reinisch et al. demonstrated that infants born to mothers treated with 10 mg/day prednisone throughout their pregnancies were "light for dates" compared with control group.
• Nevertheless, most studies of large groups exposed to GCS show no significant increase in morbidity and mortality.
• Need to take into account the high-risk nature of the diseases requiring steroids and other drugs taken simultaneously.

 

THERAPEUTIC GUIDELINES

Acute Dosage Options

• Muchos GCS is given as a single oral daily dose in the morning with an intermediateduration GCS such as prednisone.
• This approximates the body's own diurnal variation.
• Divided doses are used for acute therapy for severe, life-threatening illness (such as pemphigus).