Malignant tumours and psoriasis: climatotherapy at the Dead Sea

In this retrospective, nation-wide cohort study, the risk of cancer was assessed for 1738 Danish patients with psoriasis subjected to climatotherapy at the Dead Sea during 1972-93, by linkage to the Danish Cancer Registry. The overall risk of cancer in patients treated at the Dead Sea (standardized incidence ratio, SIR = 1.59) was higher than that expected in the general population, owing to an excess risk of non-melanoma skin cancer (NMSC) [SIR = 4.2 for basal cell carcinoma (BCC) and 10.7 for squamous cell carcinoma (SCC)]. In addition, the distribution of NMSC among body sites, age groups and sexes was unusual in those treated at the Dead Sea, favouring NMSC in young individuals and at multiple sites (SIR = 10.7 for BCC and 57.2 for SCC), multiple BCCs being particularly common among young women. Thus, people subjected to climatotherapy at the Dead Sea for psoriasis constitute a high-risk group for NMSC, SCC in particular, but not for malignant diseases in general. The study design precludes conclusions on whether climatotherapy plays a specific part in skin carcinogenesis which is different from other sources of ultraviolet (UV) radiation, as climatotherapy is inevitably confounded by excess UV exposure.     

Use of 5% imiquimod cream in the treatment of facial basal cell carcinoma: a 3-year retrospective follow-up study

There has been considerable research into the safety and efficacy of topical 5% imiquimod cream for the treatment of skin cancers in recent years, in particular superficial and nodular basal cell carcinomas. However, there are limited long-term follow-up studies. This retrospective study aims to determine the efficacy of 5% imiquimod cream in the treatment of facial basal cell carcinomas over 3 years. Medical records of 12 patients treated with 5% imiquimod cream at a private dermatology practice during 2001 and 2002 were retrospectively reviewed. Target tumours included superficial and nodular basal cell carcinomas, giving a total lesion number of 19. Patients were commenced on a once daily treatment regimen for up to 9 weeks, and given rest periods as required according to the severity of application site reactions. We found that 5% imiquimod cream is an effective treatment option for superficial and nodular basal cell carcinomas, giving a clearance rate of 89.5% at an average of 39 months of follow up.     

An open-label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.     

Malignant transformation of leg ulcers: a retrospective study of 85 cases

Background  Malignant transformation remains a rare, under-recognized and ominous, complication of leg ulcers, although its exact prevalence is unknown.
Patients and methods  This retrospective French study included cases of chronic ulcers of vascular origin complicated by histologically proven carcinomas. For squamous cell carcinomas (SCC), the duration of the ulcer had to be longer than 3 years. For basal cell carcinomas (BCC), a negative previous biopsy of the ulcer was considered.
Results  Eighty patients, accounting for 85 tumours, were included, with a female : male ratio of 2.5 : 1 and a mean age of 75 years. Eighty-eight percent of the ulcers were of venous origin and their mean duration was 27.5 years. Five patients developed bilateral cancers. Clinical findings included abnormal granulation tissue in 76% of cases, absence of healing in 14% and unusual extension in 6%. Histologically, 83/85 (98%) of tumours were SCC, among which 82% were very well or well differentiated and 18% moderately or poorly differentiated. The two remaining cases were BCC. The overall death rate was 32%; it was higher when lymph-node (66%) or visceral metastases (83%) were present. Leg amputation was performed in 29/51 (57%) of patients, irrespective of the degree of histological differentiation. For well-differentiated (grade I) and localized (stage Ia) SCC, simple surgical excision was preferred to amputation.
Conclusion  Malignant transformation of chronic leg ulcers of vascular origin is mainly encountered in elderly patients and manifests as an abnormally vegetating lesion, which may be occasionally bilateral. Malignant transformation usually occurs towards well-differentiated SCC and only exceptionally towards BCC. The high death rate, especially in metastatic cases, is at least partly due to delay in diagnosis. Surgery remains the treatment of choice. Leg amputation should be considered in the most extensive cases.     

Accuracy in the Clinical Diagnosis and Pattern of Malignant Melanoma at a Dermatological Clinic

The diagnostic pattern of malignant melanoma and clinical suspicion rate has been investigated at a dermatological university clinic. Of 174 histologically proven malignant melanomas, 60 (34%) were not clinically suspected as melanomas. The accuracy of clinical diagnosis increased with level of experience. Physicians with <1 year experience in dermatology were able to detect malignant melanoma as the first diagnosis in 31% of the cases in contrast to 63% for those with >10 years experience. Of 50 patients immediately referred from the dermatologic clinic to surgery departments, 12 did not have melanoma.     

Melanoma/skin cancer screening in a Mediterranean country: results of the Euromelanoma Screening Day Campaign in Greece

Background Since the year 2000 a melanoma/skin cancer screening campaign has been organized annually in Greece in the context of the Euromelanoma Screening Day Campaign. Objectives We aimed to analyse the characteristics of the screened population, to recognize relevant risk factors and to identify the cases of histologically confirmed malignant melanoma (MM) in individuals with suspicious skin lesions. Methods An analysis of the completed screening forms from the years 2000–2004 was performed with respect to relevant demographic, epidemiological and clinical data. Results A total of 9723 individuals were screened, most of whom where below the age of 50 years (71%), female (59%), and of skin phototype II and III (76%). Sunburn during childhood was reported in 47% of participants, while 5% of the screened population had a personal or family history of melanoma. On clinical examination, 14.4% had actinic keratoses, 31.2% had dysplastic nevi, while 6.4% carried a presumptive diagnosis of non‐melanoma skin cancer. In the 2003–2004 screening campaign, 19 out of the 171 clinically suspicious lesions were histologically proven to be MM, the majority of which (58%) were ‘thin’ melanomas (Breslow's thickness of ≤ 1 mm) of the superficial spreading type. Conclusions Our study suggested that, a melanoma/skin cancer screening programme in a Mediterranean country, supported by an intense publicity campaign, attracted many individuals at risk for skin cancer and detected mostly thin melanomas of the superficial spreading type.     

Prevalence of metabolic syndrome in patients with psoriasis: a hospital-based case-control study

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with an increased cardiovascular risk. Metabolic syndrome is a significant predictor of cardiovascular events. OBJECTIVE: To investigate the prevalence of metabolic syndrome in patients with psoriasis. METHODS: We performed a hospital-based case-control study on 338 adult patients with chronic plaque psoriasis and 334 patients with skin diseases other than psoriasis. RESULTS: Metabolic syndrome was significantly more common in psoriatic patients than in controls (30.1% vs. 20.6%, odds ratio 1.65, 95% confidence interval 1.16-2.35; P = 0.005) after the age of 40 years. Psoriatic patients also had a higher prevalence of hypertriglyceridaemia and abdominal obesity, whereas hyperglycaemia, arterial hypertension and high-density lipoprotein cholesterol plasma levels were similar. Although psoriasis patients were more frequently smokers, the association of psoriasis with metabolic syndrome was independent from smoking. There was no correlation between severity of psoriasis and prevalence of metabolic syndrome. Psoriatic patients with metabolic syndrome were older and had a longer disease duration compared with psoriatic patients without metabolic syndrome. CONCLUSION: Psoriatic patients have a higher prevalence of metabolic syndrome, which can favour cardiovascular events. We suggest psoriatic patients should be encouraged to correct aggressively their modifiable cardiovascular risk factors.     

Animal models of psoriasis: a critical appraisal

Abstract:  Although there is no naturally occurring disorder in laboratory animals that mimics the complex phenotype of psoriasis, a large number of spontaneous or genetically engineered mutations in rodents, immunological reconstitution approaches or xenotransplantation models have shed light on specific aspects implicated in the pathophysiology and therapy of psoriasis. Animal models have helped to elucidate functions of inflammatory mediators or to unravel the contribution of innate or adaptive immune mechanisms, keratinocytes or endothelial cells to chronic hyperproliferative inflammatory skin disorders. However, given that several distinct manipulations of molecular pathways, resident cutaneous cell types or immigrating immunocytes result in remarkably similar phenotypes in experimental animals, it appears that interfering with cutaneous homeostasis in general may ultimately initiate a rather uniform reaction pattern that mirrors some features of psoriasis. This limitation of animal models generated without the use of human material may, at least in part, be overcome by xenotransplantation of human skin onto immunocompromised animals. The latter approach has been employed in preclinical investigations to study the role of immune cells and/or to predict the efficacy of some therapeutic compounds. This brief review delineates approaches to generate animal models of psoriasis and discusses their strengths and limitations for psoriasis research.     

Digoxin use and following risk of psoriasis: A population-based cohort study in Taiwan

This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.     

Severe combined immunodeficiency mouse-human skin chimeras: a unique animal model for the study of psoriasis and cutaneous inflammation

Elucidation of the molecular and cellular mechanisms responsible for the pathogenesis of psoriasis had been significantly handicapped due to lack of an ideal animal model. To overcome this hurdle several investigators have developed a number of animal models for psoriasis. Recent establishment of the SCID-human skin chimeras with transplanted psoriasis plaques has opened new vistas to study the molecular complexities involved in psoriasis. This model also offers a unique opportunity to investigate various key biological events such as cell proliferation, angiogenesis, homing in of T cells in target tissues, neurogenic inflammation and cytokine/chemokine cascades involved in an inflammatory reaction. The SCID mouse model will be of immense help to target the cellular and molecular events associated with these pathogenic processes and develop novel drugs for psoriasis and other inflammatory diseases. In this article we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.     

PUVA and cancer risk: the Swedish follow-up study

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.     

Erythema annulare centrifugum-type psoriasis: a particular variant of acute-eruptive psoriasis

A case of erythema annulare centrifugum-type psoriasis in a 58-year-old white woman with a history of chronic plaque psoriasis is described. Initial failure of antipsoriatic treatments and an untypical histology complicated the diagnosis. After several trials acitretin at a low maintenance dose combined with oral fish oil and topical calcitriol led to sustained long-term remission. The spectrum of clinical differentiation of this rare disease, the histological characteristics and its nosological classification are discussed. It is suggested that this dermatosis represents a variant of acute psoriasis, rather than a variant of pustular psoriasis.     

Squamous cell carcinoma in situ of the skin: history, presentation, biology and treatment

Squamous cell carcinoma in situ (SCCIS) of the skin is a problem commonly dealt with by dermatologists. The classic presentation, originally described by Bowen, is easily recognized, but presentation on some anatomical surfaces may be associated with less than typical features. Major aetiological factors for this disease are UV light, human papillomavirus infection and immunosuppression. The natural course of SCCIS is usually prolonged, with treatment being appropriate, but not urgent. The choice of therapy requires consideration of the location of the lesion, and a desire for a high cure rate without causing loss of form, function or cosmesis. The immunomodulatory agent imiquimod has offered a significant advance for the topical treatment of SCCIS. Our improved understanding of the underlying biology of SCCIS permits us to make rational choices of treatment. In the future we may be able to determine which of these lesions may progress to invasive disease, and help us select the most effective therapy.     

Optimized UVB treatment of psoriasis: a controlled, left-right comparison trial

In a randomized, controlled, left-right comparison study, 20 patients with chronic plaque psoriasis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dose increments, the other side was given UVB doses according to measurements of skin pigmentation. Skin pigmentation was quantified by the skin reflectance technique. The relationship between skin pigmentation and sensitivity to UV radiation was used to optimize and individualize the initial UVB exposure dose. Clinical outcome, initial, final and cumulative UVB doses, time to 50% reduction in PASI score, and side-effects were compared. The consequence of the optimization of the UVB doses with a skin reflectance meter was that the initial UVB dose was significantly higher than in the conventional UVB regimen. PASI scoring demonstrated a more rapid improvement during the first 2 weeks of treatment on the half body receiving the optimized treatment compared to the other side (P < 0.05). This new technique offers the same therapeutical advantages and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a quick method which can be operated easily by nurses.     

Superimposed linear psoriasis: a historical case revisited

In 1978, a case of “ichthyosis vulgaris and ILVEN syndrome (inflammatory linear verrucous epidermal nevus)” was presented by Johannes Ring, of Munich [ 1 ]. Based on present knowledge, a diagnosis of superimposed linear psoriasis appears simpler and more appropriate because the 10‐year‐old girl also had multiple psoriatic plaques, with a symmetrical and non‐segmental distribution. The linear manifestation most likely reflects the clonal outgrowth of a population of cells harboring a postzygotic mutation that increased the predisposition to psoriasis.     

Psychiatric morbidity in psoriasis and vitiligo: a comparative study

The psychiatric morbidity in psoriasis patients was compared with that in vitiligo patients using the standardised Hindi (vernacular language) version of the General Health Questionnaire (GHQ-H). Thirty new and untreated patients each with psoriasis or vitiligo and between the ages of 18-60 yrs, constituted the study group. The prevalences of psychiatric morbidity as assessed by the GHQ-H were found to be 53.3% and 16.22% in the psoriasis and vitiligo patients respectively; the difference was statistically significant (p=0.0028). The prevalences of depression were 23.3% and 10% in psoriasis and vitiligo respectively and anxiety was observed in 3.3% of each group. Sleep disturbance was the most common complaint and was present in 56.6% of psoriasis patients and 20% of the vitiligo patients. However, the parameter of sleep disturbance showed a statistically significant difference between the two dermatoses (p=0.0034).     

The lipid profile in psoriasis: a controlled study

BACKGROUND: Psoriasis is an inflammatory dermatosis that is characterized with hyperproliferation of keratinocytes and inflammatory infiltration in the epidermis and dermis. The high prevalence of atherosclerosis has been reported in psoriatic patients. High serum lipid level has been suggested in the pathogenesis of this phenomenon. In this study, our purpose was to compare the lipid profile in psoriatic patients with non-affected persons. METHODS: This study was designed and conducted as a case-control assay with 50 cases in the patient and control groups, respectively. The lipid profile, including serum level of triglyceride, cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), were assessed in both groups. RESULTS: The patient and control groups each consisted of 50 cases (39 male and 11 female). The serum triglyceride, cholesterol, and LDL was significantly higher in psoriatic patients (P < 0.05) but not for HDL (P = 0.29). CONCLUSION: This study, like previous assays, shows that high serum lipid level is significantly more common in psoriasis. This fact may be responsible for higher prevalence of cardiovascular accident in psoriatic patients. It may be useful to do early screening and treatment of hyperlipidaemia in psoriasis to prevent the atherosclerosis and its complications.     

The impact of changes in clinical severity on psychiatric morbidity in patients with psoriasis: a follow-up study

BACKGROUND: Psoriasis has a strong impact on quality of life and is correlated to psychopathological states. It is important to investigate the effect of clinical changes on psychological status. OBJECTIVES: To analyse the extent of clinical change and its effect on the presence of psychiatric morbidity in a group of patients with psoriasis. METHODS: All eligible adults hospitalized with psoriasis in a dermatological hospital (February 2000-February 2002) were given the self-administered Psoriasis Area and Severity Index (SAPASI) to assess clinical severity, the 12-item General Health Questionnaire (GHQ-12) to detect patients with psychological problems (defined as 'cases') and the Skindex-29 to evaluate symptoms. The same questionnaires were completed by the patients a month after hospital discharge. RESULTS: In our population of 414 patients, the incidence of GHQ cases becoming noncases was correlated with the SAPASI percentage improvement, ranging from 17.6% in patients with SAPASI worsened or unchanged at follow-up, to 68.2% in patients with clearance of psoriasis. Also, the proportion of patients who became GHQ noncases was much higher in patients with improvement of >/= 50% in symptoms, compared with patients with no improvement or worsening (70% vs. 32%, respectively). In a multivariate model the possible determinants of the passage from GHQ case to noncase were: SAPASI improvement, symptom improvement, no localization on the face, and gender (i.e. women were less likely to improve psychologically). CONCLUSIONS: The improvement in clinical severity and symptoms was associated with a decreased frequency of psychiatric disturbance. However, dermatologists should be aware that even in the presence of vast clinical improvement patients may still substantially suffer psychologically.