Biomedical subjects
Publications and source records attributed to E M Farber.
This article reviews the history of selected therapeutic agents for psoriasis: arsenic (including Fowler's solution), ammoniated mercury, chrysarobin and anthralin, tars, aminopterin and methotrexate, and corticosteroids. The developers of these drugs paved the way for the new and improved treatments available today for the treatment of psoriasis.
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Psoriasis of the genitalia occurs in all age groups from infancy to the elderly. Approximately one-quarter to one-half of various epidemiologic studies report that genital psoriasis occurs with a higher frequency in males than in females. Therapeutic modalities for management of psoriasis in this site underscore the need for caution in not irritating the sensitive genital skin. Preventive measures include avoiding tight under- and outer-garments that provoke penile or vulvar psoriasis as well as maintaining cleanliness of the genital area.
Psoriasis of the perianal and intergluteal areas can cause pain and discomfort. Individualized therapeutic programs will reduce the morbidity. It is essential that optimal hygienic conditions be maintained in these regions to avoid itching and inflammation.
Nonpustular palmoplantar psoriasis can be disabling in causing painful fissuring and scaling. Preventive measures in avoiding friction and irritants can reduce the morbidity of this variant. Lubricants, anthralin, and corticosteroids form the mainstay of therapy in mild and moderate psoriasis of the palms and soles. Topical PUVA therapy and use of cytotoxic agents should be reserved for refractory cases.
Psoriasis of the ears occurs in approximately 18 percent of all patients at some time. Prevention by avoidance of picking and scratching and careful cleansing are helpful. Treatment with intralesional injection of triamcinolone acetonide is effective in patients resistant to other therapies.
The face has been cited as being the least affected body surface in patients with psoriasis. It also has been reported that psoriasis of the face is more prevalent in children than in adults, and when it does occur, at any age, the face is never the only body part involved. In fact, face involvement may reflect a high degree of severity of psoriasis.
Psoriatic nail involvement is common and accompanies skin lesions on the body surface. The occurrence of nail psoriasis has been reported in up to 50 percent of patients, including children, adults, and the elderly. The characteristics of psoriatic nails are pitting, discoloration, onycholysis, subungual hyperkeratosis, as well as crumbling and grooving of nails and splinter hemorrhages. There is no consistently effective treatment for psoriatic nail involvement; nails are difficult to treat and respond slowly to therapy. Corticosteroids, 5-fluorouracil, systemic agents such as photochemotherapy, oral retinoids, and methotrexate, and nail avulsion are among the therapeutic approaches utilized. We offer suggested measures whereby patients may benefit in the prevention and control of their nail psoriasis.
The scalp is a common site of involvement at onset and throughout the course of psoriasis. Worldwide census studies report that approximately half of the psoriasis population are afflicted with psoriasis of the scalp. We describe the frequency, clinical aspects, and treatment of scalp psoriasis in childhood, adulthood, and in the geriatric age groups. Measures of prevention and control are reviewed.
In each of 14 patients, two small but comparable psoriatic lesions were infused for 2 weeks with either saline or a saline solution of peptide T (as its analog D-ala1-peptide T amide) at 10(-7) mol/L with Alzet osmotic pumps worn extracorporeally. During infusion, lesions were photographed and scored for clinical features of psoriasis on a 9-point scale. After another 7 days, biopsy specimens were taken from the infused sites, and sections were scored for features of psoriasis on a 19-point scale. The differences between means for data from saline- and peptide T-infused lesions were evaluated statistically. Peptide T-infused lesions improved clinically; scores decreased from a mean of 4.35 initially to 1.57 at biopsy, whereas control lesions changed from 4.43 to 3.57 (p less than 0.01 for 1.57 vs 3.57). Histologic scores were also significantly different (5.28 for peptide T vs 10.00 for controls, 0.05 greater than p greater than 0.02). This study provides evidence that intralesionally infused peptide T demonstrates some clearing effect in psoriasis.
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The use of high-dose electron-beam therapy for mycosis fungoides at Stanford University is reviewed. Since 1966, 140 patients have been treated in this fashion. Their clinical characteristics including initial extent of disease are reviewed. The results of routine staging studies are examined. Eighty-four percent of the patients achieved an initial complete remission; this was inversely related to the initial extent of skin involvement. The overall survival rate was 46% at 10 years with the major prognostic factor being the initial extent of skin involvement. Other factors which had an influence on the patient's progrnosis included the presence of palpable adenopathy, the patient's age, the achieving of an initial complete remission, the initial dose of electron-beam therapy, and the treatment with adjuvant topical mechlorethamine. The development of a rationale for the treatment of patients with all stages of mycosis fungoides based upon these clincal observations is discussed.
Human Major Histocompatibility (HLA) complex antigens B13, BW16, BW17, CW6 and D-MA are increased in frequency in patients with psoriasis. Of these, the strongest association is with HLA-CW6 and D-MA, with a relative risk of 10.4. Since no strong association with any HLA-A locus antigen is seen, it seems likely that the disease susceptibility gene for psoriasis lies close to the HLA-D locus, which is defined by the use of the mixed lymphocyte reaction (MLR). In the mouse, the Immune response (Ir) genes are found in the MLR region and it is thought that Ia antigens lie at a corresponding location in man. Recently, we have demonstrated that human epidermal cells cause stimulation in the mixed lymphocyte reaction. Lymphocyte antigens which stimulate in this reaction are known to be products of HLA genes and anti-HLA-D sera block stimulation by epidermal cells. It is possible that these antigens may be involved in the regulation of cell--cell communication. Psoriasis is a disease characterized by epidermal hyperproliferation. It is possible, therefore, that an HLA-linked deficiency of recognition between epidermal cells exists in patients with psoriasis and that this defect allows abnormal cellular proliferation to occur.
Polyamine metabolism is important in cell proliferation and may play a role in the epidermal cell hyperproliferation of psoriasis. We have determined changes in polyamine levels in skin and urine accompanying clinical improvement in psoriasis following topical therapy. Nine hospitalized patients were examined at the beginning and end of their courses of treatment. Skin biopsy specimens and portions of 24-hour urine collections were analyzed for polyamines with a modified automatic amino acid analyzer. Treatment resulted in lower cutaneous levels of putrescine (by 50%, P less than .05), spermidine (by 24%, P less than .05), and spermine (by 35%, P less than .005), and lower urinary levels of spermidine (by 20%, P less than .025) and spermine (by 35%, P less than .025). These results suggest that in psoriasis, the skin significantly contributes to the levels of spermidine and spermine in systemic fluids. Topical therapy may reduce epidermal cell proliferation in psoriasis by lowering polyamine levels.
The frequency of two newly defined HLA antigens, HLA CT7 and DMA, was found to be greatly increased in patients with psoriasis. These two antigens and those previously found to be associated with the disease, B13, BW16 and BW17, frequently occurred together. The disease may be primarily associated with HLA DMA, or with the HLA haplotypes CT7--B13/W16/W17--DMA.