A simple clinical scoring system to improve the sensitivity and standardization of the diagnosis of mycosis fungoides type cutaneous T-cell lymphoma: logistic regression of clinical and laboratory data.

BACKGROUND: The diagnosis of mycosis fungoides (MF) is notoriously difficult to establish because in the early stages, histological features may be nonspecific or merely suggestive. OBJECTIVES: To standardize the diagnosis of MF. METHODS: We studied 138 patients with suspected MF referred over a 7-year period to a university department of a dermatology-based cutaneous lymphoma clinic. Six diagnostic criteria were evaluated: clinical morphology, clinical distribution, skin biopsy T-cell receptor gene rearrangement (TCR-GR), skin biopsy pan T-cell marker loss > or = 2, skin biopsy CD4/CD8 ratio > or = 6, and skin biopsy diffuse epidermal HLA-DR expression. These six clinical and laboratory criteria were compared by logistic regression analysis in patients with histologically diagnosed MF and those with benign disease. RESULTS: Of the 138 patients, 74 had histology of MF, 47 of benign dermatoses and 17 were indeterminate. Close associations were found between a histological diagnosis of MF and TCR-GR (odds ratio 14.4), classical morphology (7.5), classical distribution (2.5) and diffuse epidermal HLA-DR expression (2.8). Logistic regression models were developed depending on the availability of data (either TCR-GR or HLA-DR). Probabilities for correctly diagnosing MF compared with histology as the 'gold standard' were derived from these logistic regression models. A scoring system assigning point values based on these probabilities was then created in order to assist the clinician in making the diagnosis. If using TCR-GR data, a positive TCR-GR = 2.5 points, the presence of classical morphology = 2.0 points, and the presence of classical distribution = 1.5 points. A total score of > or = 3.5 points assigns a high probability (> 85%) of having MF. If using HLA-DR expression, then the presence of classical morphology = 2.5 points, a positive diffuse epidermal HLA-DR expression = 2.0 points, and the presence of classical distribution = 1.5 points. In this case, a total score of > or = 4.0 points assigns a high probability (> 85%) of MF. CONCLUSIONS: The logistic regression models and scoring systems integrate clinical and laboratory assessments, allow rapid probability estimation, and provide a threshold for the diagnosis of MF in an objective, standardized manner.

Reliability of wound measuring techniques in an outpatient wound center.

Wound measurements determine whether treatment(s) should be continued or changed. A busy wound clinic must rely on many different personnel for wound measurements. The realization that using a variety of measurement techniques could effect medical treatment choices raised concerns. To determine the inter-rater reliability of wound measuring techniques used by clinical staff in an outpatient wound center, three approaches to wound measurement were studied with the intent to standardize clinic procedures in the authors' facilities and to use the method with greatest inter-rater reliability. An exploratory descriptive study was initiated in a busy multidisciplinary wound-healing clinic in a northeastern Ohio 500-bed teaching and community hospital. Participants included 16 wound care professionals who staff an outpatient wound center. Inter-rater reliability measures were compared to three measurement techniques. The intraclass correlation coefficient was used as the statistical measure of inter-observer agreement. After comparing measurements made by the usual method used by an individual, the clockwise method, and the perpendicular method, the perpendicular method showed clear superiority in agreement among clinicians (ICC .962; df = 11,143; P = < 0.001) as compared to the clock-wise method (ICC .682; df = 11,154; P = < 0.05). This study provided a basis for standardizing the approach to wound measurement among physicians and nursing personnel and has important implications for effective medical care, research, and healthcare cost savings.

Skindex, a quality-of-life measure for patients with skin disease: reliability, validity, and responsiveness.

To measure the effects of skin disease on patients' quality of life, we developed a 61-item self-administered survey instrument called Skindex. Skindex has eight scales, each of which addresses a construct, or an abstract component, in a comprehensive conceptual framework: cognitive effects, social effects, depression, fear, embarrassment, anger, physical discomfort, and physical limitations. Item responses are standardized from 0 (no effect) to 100 (maximal effect); a scale score is the average of responses to items addressing a construct. In 201 patients seen by dermatologists, mean scale scores (+/-SD) ranged from 14 (+/-17) for physical limitations to 31 (+/-22) for physical discomfort. Scale scores were reproducible after 72 h (r = 0.68-0.90) and were internally consistent (Cronbach's alpha = 0.76-0.86). Construct validity was assessed in two ways: (i) in a comparison of patients with inflammatory dermatoses and patients with isolated lesions, patients with inflammatory dermatoses had higher scale scores, and (ii) in an exploratory factor analysis, 78% of the common variance was explained by seven factors that correlated with the scale scores of Skindex. Most of the a priori scale scores changed in the expected direction in patients who reported that their skin conditions had improved or worsened after 6 mo. Finally, physicians' judgments of disease severity did not consistently correlate with Skindex scores. These preliminary data suggest that Skindex reliably and responsively measures the effects of skin disease on patients' quality of life and may supplement clinical judgments of disease severity.

Role of epidemiology in occupational dermatology.

The role of epidemiology in occupational dermatology is multifaceted, but the goal is to gain useful information from looking at defined populations. Useful information means that the results of observation or study of that population are sufficiently unbiased to be true (valid) for the study population as well as for individuals with similar circumstances (e.g., risk factors or exposures) who were not part of the study (generalizability). The future of epidemiology in occupational skin diseases includes analyzing ongoing studies, developing new studies, and setting up programs for surveillance and screening. There will also be continuing interaction among industry, government, attorneys, and clinicians. Much useful data can be obtained using computers and establishing databases; but the data will be most useful if some of the epidemiologic concepts described are followed. Dermatologists should be encouraged to learn more about epidemiology and to use its methods to enhance both their practice and the quality of studies they may contribute to the medical literature.

Complete remissions in psoralen and UV-A (PUVA)-refractory mycosis fungoides-type cutaneous T-cell lymphoma with combined interferon alfa and PUVA.

UNLABELLED: BACKGROUND AND DESIGN--The optimal therapy for the mycosis fungoides type of cutaneous T-cell lymphoma has yet to be determined. Based on recent reports on the efficacy of high-dose interferon alfa in cutaneous T-cell lymphoma, we chose to test the hypothesis that systemic adjunctive therapy with low-dose interferon alfa along with psoralen and long-wave UV-A radiation (PUVA) could decrease the amount of PUVA necessary to achieve the best response, as well as improve the therapeutic effect of PUVA. Five patients with cutaneous T-cell lymphoma (mycosis fungoides type) were initially treated unsuccessfully with PUVA alone (three times a week for at least 3 months); PUVA was stopped, patients' diseases were re-staged, then interferon alfa (3 x 10(6) U/d for 1 week, then 6 x 10(6) U/d for 1 week) was initiated 2 weeks prior to restarting PUVA. Responses to treatment were graded as complete remission (skin clear, or negative biopsy specimens of remaining dermatitic lesions), partial remission (> 50% improvement), progression (> 25% worsening), or no change (failure to qualify for other categories) at 4, 8, 12, and 16 weeks. OBSERVATIONS--After 3 to 5 months of treatment with PUVA thrice weekly, none of the patients treated with PUVA alone had achieved complete remission. By contrast, systemic adjunctive therapy with low-dose interferon alfa along with PUVA resulted in complete remissions in all five (100%) patients in an average of 3.2 months (in three patients, lesions were cleared by 3 months). Average of 107 additional joules (68% more) and 1.6 additional months of PUVA administered thrice weekly was required to achieve the best response attainable with PUVA alone compared with complete remissions achieved with combined interferon alfa and PUVA therapy. CONCLUSION: --These data indicate that patients with disease refractory to PUVA alone can achieve a complete remission if they restart treatment with PUVA in combination with well-tolerated low doses of interferon alfa. In addition, the duration of PUVA exposure can be reduced with the addition of low-dose interferon alfa to the conventional PUVA treatment of cutaneous T-cell lymphoma of the mycosis fungoides type in such patients.

Smoking habits in survivors of childhood and adolescent cancer.

Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in data collected from 1289 adult survivors of childhood cancer and 1930 of their sibling controls. Survivors were diagnosed with cancer between 1945 and 1974 when they were less than 20 years old. Using matched analyses that controlled for the influence of family, survivors were 8% less likely than controls to be current smokers, 13% less likely to be ever-smokers, but 12% less likely to have quit smoking; these differences were not statistically significant. In a logistic regression analysis there was a significant difference by year of diagnosis for current smoking rate ratios (RR); survivors were less likely to be current smokers if diagnosed in recent years (RR = 0.76; 95% confidence intervals = 0.58-0.98, between 1965-74) and quite similar to controls if diagnosed in earlier years (RR = 1.05 between 1945 and 1954). In our group of long-term cancer survivors, the reduction in current smoking came about because survivors were more inclined never to start smoking than controls. Once addicted to tobacco, they were less likely to quit. While the fact that survivors are less likely to start smoking is encouraging, the persistence of smoking habits strongly suggests the need for continuing efforts to prevent smoking in this most vulnerable group.

Quality of life in long-term survivors of CNS tumors of childhood and adolescence.

Clinical reports of small numbers of pediatric brain tumor patients observed for brief periods suggest that long-term survivors continue to have major handicaps into adulthood. To quantify these late effects we interviewed 342 adults (or their proxies) who had CNS tumors diagnosed before the age of 20 between 1945 and 1974, survived at least 5 years, and reached 21 years of age. Survivors were 32 years old on average at follow-up. When compared with 479 matched siblings as controls. CNS tumor survivors were more likely to have died or to have become mentally incompetent sometime during the follow-up period. They were more likely to be at risk for such adverse outcomes as unemployment (odds ratio [OR], 10.8; 95% confidence interval [CI], 4.6 to 25.7], to have a health condition that affected their ability to work (OR, 5.9; CI, 3.7 to 9.4), to be unable to drive (OR, 28.8; CI, 6.9 to 119.9), or to describe their current health as poor (OR, 7.8; CI, 1.7 to 35.7). Unfavorable outcomes were more frequent in male survivors than in females, in those with supratentorial tumors compared with infratentorial ones, and in those who received radiation therapy. As clinicians consider improving therapies, they should anticipate late effects, such as those we observed, and attempt to target subgroups for interventions that may improve subsequent quality of life.

A case-control study of cancer of the endometrium.

A hospital-based case-control study of the epidemiology of endometrial cancer in women aged 45-74 years was carried out in Connecticut from 1977 to 1979. In total, 167 cases and 903 controls were included. Elevated risks were associated with the following factors: overweight, nulliparity, few pregnancies, use of estrogen replacement therapy, older age at menopause, and a history of ovarian or endometrial cancer in mother or a sister. Whites were more frequently affected than blacks, and better-educated women more often than less-educated women. Use of oral contraceptives was associated with a decreased risk, although the decrease did not reach statistical significance.

PIP: A case-control study of the epidemiology of endometrial cancer in women aged 45-74 years was carried out in 7 hospitals in Connecticut from 1977-79. 167 cases of adenocarcinoma, adenocanthoma, and adenosquamous neoplasms of the endometrium were included. 903 women of the same age admitted to surgical services except gynecology served as controls. Response rates were 67% for cases and 72% for controls. Odds ratios for the association between selected variables and endometrial cancer, adjusted by linear logistic regression for the effect of all other variables in the table, indicated that elevated risks were associated with being white and being well-educated, among demographic variables, and with nulliparity, fewer pregnancies, later age at menopause, use of estrogen replacement therapy, and a history of ovarian or endometrial cancer in mother or a sister, among reproductive variables. The longer estrogen replacement therapy was used, the higher the risk, up to 10 years of use. Heavier women were found to be at higher risk, although the risk for women of medium weight was only slightly increased. Women who reported a history of diabetes had a somewhat increased risk, while a history of ever having blood clots in the veins or of having had tubes tied was associated with reduced risk. Use of oral contraceptives was associated with a decreased risk, although the decrease did not reach statistical significance.

Effect of age at first childbirth on risk of developing specific histologic subtype of breast cancer.

Epidemiologic variables related to breast cancer risk were assessed in a case-control study of 332 women with breast carcinoma and 1353 comparison women. Risk factors for breast cancer as a whole included nulliparity, late age at first childbirth, early age at menarche, late age at menopause, personal history of benign breast disease, family history of breast cancer, and among postmenopausal women, body weight. These risk factors were then analyzed with respect to histologic subtype of breast cancer involved, i.e., duct-derived or lobular tumors, to determine whether the association between any of the risk factors and breast cancer varied according to histopathologic subtype. Histologic subtype for the 316 cases reviewed included 284 duct cancers and 32 lobular carcinomas. Although slight differences were noted among some of the risk factors and the variety of cancer, none of the differences was marked except for the variable age at birth birth. For ductal carcinoma, the risk was highest among nulliparous women and decreased the younger a woman was at the time she gave birth to her first child. The risk of infiltrating lobular carcinoma, however, was lowest among nulliparous females or those who had given birth at a young age and increased the older a woman was when she gave birth to her first child.

An epidemiologic study of epithelial carcinoma of the ovary.

A case-control study to identify risk factors for epithelial ovarian cancer was undertaken among women in the age group 45-74 years who had been admitted to seven hospitals in Connecticut between July, 1977, and March, 1979. Characteristics that were found to increase the risk of epithelial ovarian cancer included being white, never having been pregnant, having a late age at menopause, having a family history of cancer of the ovary or endometrium, and having a long estimated number of years of ovulation. Prior use of post-menopausal estrogens did not alter the risk for epithelial ovarian cancer, but there was some indication that oral contraceptives protect against ovarian cancer. Women with ovarian cancer were somewhat more likely to have had a history of an underactive thyroid and were somewhat less likely to have had a history of an overactive thyroid than controls, although these trends were not statistically significant.

Exogenous estrogens and other factors in the epidemiology of breast cancer.

In a hospital-based case-control study of the epidemiology of breast cancer undertaken in Connecticut from 1977 to 1979, there was no evidence of an increase in risk for breast cancer among women who had used oral contraceptives or estrogen-replacement therapy. In fact, there was some suggestion of a decrease in risk for breast cancer with increasing length of use of oral contraceptives. Higher than average risks were found among women who had never give birth to a child, women with a late age at menopause, women, with an early age at menarche, women who had given birth to their first child at a relatively late age, women with previous benign breast disease, and women with a history of breast cancer in a sister or mother. Heavy women were at high risk for premenopausal breast cancer. The association between heaviness and postmenopausal breast cancer was strongest among women who had had their last menstrual period more than 5 years before the diagnosis of breast cancer.

Work role and depression in women: a comparison of workers and housewives in treatment.

Comparison of a patient population of depressed housewives with a matched group of depressed working women revealed some significant differences in social functioning in relation to work roles. The psychological benefits of outside employment have been widely discussed in relation to middle-class and upper-class women; this study indicates that, for women of lower socio-economic status, work may also have a protective psychological effect.