Diltiazem induces severe photodistributed hyperpigmentation: case series, histoimmunopathology, management, and review of the literature.

BACKGROUND: Diltiazem hydrochloride is a commonly prescribed benzothiazepine calcium channel blocker for the treatment of cardiovascular disease. Recently, 8 cases of diltiazem-induced photodistributed hyperpigmentation occurring predominantly in elderly African American women were reported. Here, we report occurrence for the first time in a light-skinned African American woman and a Hispanic woman. We also report this finding in an African American man. Biopsy specimens of hyperpigmented areas were obtained for histopathologic evaluation and marker studies. Photospectrometry analysis for diltiazem was performed to analyze the photoabsorption properties of this drug. OBSERVATIONS: Routine laboratory examination results were normal in all patients. Serologic test results for antinuclear antibodies, including Sjögren antibodies anti-Ro (SS-A) and anti-La (SS-B), were negative. Histopathologic analysis of the skin biopsy specimens revealed a sparse lichenoid infiltrate, prominent pigmentary incontinence, and numerous melanophages in the dermis. There was no increase in dermal mucin suggestive of lupus. The mononuclear cells in the specimens were strongly positive for CD3, weakly positive for CD68, and either weakly positive or negative for CD79a. All specimens were negative for Alcian blue staining. Photospectrometry analysis of diltiazem showed an absorption range within the UV-B spectrum. CONCLUSIONS: Photospectrometry analysis revealed diltiazem could demonstrate a photosensitizing effect within the UV-B range. Discontinuation of therapy with diltiazem is the most effective modality in resolving hyperpigmentation. Avoidance of sun exposure and consistent use of sunscreens and sun-protective clothing are indicated for patients undergoing diltiazem therapy.

Effects of ultraviolet B exposure on the expression of proliferating cell nuclear antigen in murine skin.

Proliferating cell nuclear antigen (PCNA) is an active nuclear protein involved in DNA replication, recombination and repair. PCNA is found throughout the basal layer in normal skin and in all layers of the epidermis in malignancy. This study evaluates PCNA's expression after acute and chronic UV-B irradiation. Skh-1 hairless mice exposed to 1.5 and 4.5 kJ/m2 of UV-B were sacrificed at 6, 12, 24, 48, 72 and 168 h. Immunohistochemical analysis revealed PCNA expression throughout the basal layer of untreated skin, with diminished expression at 6 h, indicative of immediate UV damage, and evidenced by the observable upregulation in pyrimidine dimer formation early on. Subsequently, PCNA immunoreactivity progressively increased, demonstrating an aberrant upward epidermal migratory pattern in association with chronic exposure. The 4.5 kJ/m2 group exhibited prolonged recovery in staining and also demonstrated this altered migratory pattern with chronic exposure. Progressive reactivation of PCNA expression occurs with repair. PCNA migration to upper layers of the epidermis indicates proliferation and possibly a subsequent increased malignant potential. We conclude that PCNA can serve as a marker of DNA repair and indirectly as an indicator of UV-B-induced damage, expression being time dependent and dose related. Specific immunoreactivity patterns and the observable atypia in keratinocytes are relevant in elucidating malignant potentiation.

Scrotal calcinosis: is the cause still unknown?

Scrotal calcinosis is a rare benign entity of calcified nodules within the scrotal skin. We describe a healthy 25-year-old man with multiple asymptomatic calcified nodules restricted to the scrotum. Histologic studies of multiple nodules showed calcium deposition, and basophilic material with sparse inflammation surrounded by a fibrous capsule. Because the intensive evaluation of our patient failed to reveal a cause, an analysis of all 123 cases found in the literature was conducted. Several plausible origins for scrotal calcinosis are disclosed; however, pathogenesis of this condition remains equivocal and controversial. The most common treatment option is excision of the affected nodules. Our report underscores the need for further investigation of this florid and bizarre disorder.

Ultraviolet radiation and skin cancer.

Skin cancer is the most common type of cancer in fair-skinned populations in many parts of the world. The incidence, morbidity and mortality rates of skin cancers are increasing and, therefore, pose a significant public health concern. Ultraviolet radiation (UVR) is the major etiologic agent in the development of skin cancers. UVR causes DNA damage and genetic mutations, which subsequently lead to skin cancer. A clearer understanding of UVR is crucial in the prevention of skin cancer. This article reviews UVR, its damaging effects on the skin and its relationship to UV immunosuppression and skin cancer. Several factors influence the amount of UVR reaching the earth's surface, including ozone depletion, UV light elevation, latitude, altitude, and weather conditions. The current treatment modalities utilizing UVR (i.e. phototherapy) can also predispose to skin cancers. Unnecessary exposure to the sun and artificial UVR (tanning lamps) are important personal attributable risks. This article aims to provide a comprehensive overview of skin cancer with an emphasis on carefully evaluated statistics, the epidemiology of UVR-induced skin cancers, incidence rates, risk factors, and preventative behaviors & strategies, including personal behavioral modifications and public educational initiatives.

Behavioral factors of patients before and after diagnosis with melanoma: a cohort study - are sun-protection measures being implemented?

Melanoma is the deadliest form of all skin cancers and is highly linked to sun-related behavior in patients. However, sun-protection behavior to prevent melanoma in this population has been shown to be inadequate to date. The objective of this study was to compare changes in sun protection habit before and after patients' diagnosis with malignant melanoma. The study also seeks patients' advice on how to improve public education on melanoma prevention. A retrospective survey study was conducted on 68 respondents of patients diagnosed with melanoma from six different dermatologic practices in various boroughs of New York and Long Island in the state of New York by telephone interviews. There was a significant positive change in patients' sun-protection behavior after they were diagnosed with melanoma. Various methods of sun protection, such as avoiding sun exposure, applying and reapplying sunscreen, and wearing protective clothing were practiced more frequently after diagnosis. In addition, the frequency of sunbathing decreased drastically. Most patients were aware about the dangers of sun exposure before their diagnosis. They, however, did not feel the need to adopt sun-protection measures before their diagnosis. Respondents advised that education on dangers to excess sun exposure should be provided at an early age through multiple venues. The study reflected that 71% of diagnosed patients who completed the survey were informed about sun protection before their diagnosis. Many patients did not follow strict guidelines to prevent sun damage as shown by their behaviors before diagnosis. Diagnosis of the disease was apparently the main motivating factor to initiate challenging behavioral changes.

Cohort study on patient response to botulinum toxin cosmetic therapy.

BACKGROUND: Botulinum toxin (BTX) therapy is currently the most popular cosmetic procedure in the United States. However, few studies exist regarding post-procedure perceptions of the patients' BTX therapy. OBJECTIVE: The aim of this cohort study was to determine patients' responses from pre- to post-BTX treatment experience. METHODS AND MATERIALS: One hundred twenty-three BTX patients of six different dermatologic cosmetic practices in various boroughs of New York and Long Island in the state of New York completed the questionnaire. Six hundred eighty-three surveys were sent out, and 123 completed surveys were obtained. Numerous questions were asked regarding how patients felt and responded towards the overall procedure of their BTX therapy. RESULTS: Eighty-eight percent of patients were satisfied or extremely satisfied with their dermatologists. Sixty-five percent of patients felt over 60% improvement in areas treated. Fifty-eight percent of patients anticipated making repeat visits, whereas the biggest concern for returning was due to the expensive cost of BTX. CONCLUSION: Our study correlated with previous studies done on retention rate of BTX cosmetic patients and satisfaction level on areas treated. The cost of BTX remained one of the primary concerns for repeat visits. Most patients were happy with their visits to the dermatology offices for BTX procedure, although things can be done to further enhance their visits and the likelihood that they will return.

Traction alopecia in Sikh male patients.

This article reports on traction alopecia among Sikh males as a result of stress on the hair from wearing a turban. Treatment for this condition in such a population is difficult. Permanent removal of the turban is religiously forbidden. Therefore, the traction continues, as will the alopecia, possibly accompanied by seborrheic dermatitis and psoriasis.

The causes of skin cancer: a comprehensive review.

Skin cancer is the most common type of cancer in fair-skinned populations around the world. The incidence and mortality rates of skin cancers are dramatically increasing and thus pose a threat to public health. Understanding the etiology and pathogenesis of skin cancer remains a goal for healthcare systems. A clearer understanding of causative factors is an essential step in the prevention of skin cancer. This article comprehensively reviews the causative agents which play a role in the development of skin cancer. Ultraviolet radiation (UV) from sun exposure is the most important cause of skin cancer. Sunburns and excessive exposures cause cumulative damage which induces immunosuppression and skin cancers. Ozone depletion, the level of UV light, elevation, latitude, altitude and weather conditions influence the emission of UV radiation reaching the earth's surface. Organ transplant recipients and AIDS patients have an increased incidence of skin cancers. Some treatment modalities, including radiation therapy, phototherapy and psoralen and long-wave ultraviolet radiation (PUVA) can also predispose to skin cancers. Viral infections such as the human papilloma virus can cause squamous cell carcinomas. Individuals with familial genetic syndromes are susceptible to specific types of skin cancers. Ionizing radiation, environmental pollutants, chemical carcinogens and work-related exposures have been associated with skin cancers. Exposure to artificial UV radiation (tanning beds and lamps), aging, skin color, diet and smoking are attributable risks. Skin cancers have been found in dermatoses and various types of keratoses, chronically injured or nonhealing wounds, and scars. This article provides a comprehensive and thorough overview of skin cancer, with an emphasis on understanding its epidemiology, incidence, etiology and related risk factors.

Idiopathic splinter hemorrhages.

Splinter hemorrhages are non-blanchable usually distal reddish-brown linear hemorrhages beneath the nails. Among a variety of etiologic factors reported, trauma is the most common cause. A 26-year-old Hispanic female presented with asymptomatic, extensive fingernail hemorrhages of two months duration. There was no history of physical trauma to the nails. Treatment with a topical antifungal medication for one month produced no improvement. The past medical history was noncontributory. Extensive laboratory testing revealed no underlying systemic disease. Three months after the initial presentation, 6 of 10 fingernails showed signs of resolution without treatment. We conclude that idiopathic atraumatic subungual splinter hemorrhages can occur in healthy individuals. Spontaneous resolution occurred in our patient.

Use of Ber-EP4 protein in recurrent metastatic basal cell carcinoma: a case report and review of the literature.

The occurrence of metastatic basal cell carcinoma (MBCC) is extremely low, ranging from 0.0028 to 0.5%. We present a rare case report of MBCC in a 57-year-old Caucasian male with a known history of numerous nonmelanoma cutaneous neoplasms. The patient presented with a large ulcerated right axillary mass that recurred 2 months after an initial BCC was resected from the same site. An excisional biopsy of the recurrent mass and regional lymph nodes showed atypical basaloid cells with hyperchromatic nuclei, stromal retraction and rare squamous features in the soft tissue and lymph node. The tumor cells were bcl-2 negative and positive for Ber-EP4. The negative expression of bcl-2 correlates with the aggressive nature of this tumor and Ber-EP4 confirmed the diagnosis of BCC.

Protective effects of lycopene against ultraviolet B-induced photodamage.

Lycopene, an acyclic hydrocarbon carotenoid found in tomatoes and their products, is a well-established potent antioxidant, and its anticancer properties have been shown in cultured cells and animal models. We investigated the protective effects of two concentrations of topical lycopene against acute ultraviolet B (UVB)-induced photodamage. Application of lycopene dose dependently inhibited UVB-induced ornithine decarboxylase (P < 0.05) and myeloperoxidase (P < 0.05) and significantly reduced bifold skin thickness (P < 0.05). Immunohistochemical staining revealed increased active caspase-3 of apoptotic pathway in the UVB-exposed group compared with the unexposed control. Application of topical lycopene prevented the cleavage of caspase-3. UVB irradiation completely diminished proliferating cell nuclear antigen (PCNA), and the untreated skin maintained positively stained cells throughout the basal epidermis. Topical application of lycopene significantly reversed UVB-induced PCNA inhibition, and normal PCNA staining was restored in the lycopene-treated skin. Our results suggest that topical lycopene is able to exert its protective effects against acute UVB-induced photodamage. Furthermore, it may act as a preventative agent via inhibition of epidermal ornithine decarboxylase activity, reducing inflammatory responses, maintaining normal cell proliferation, and possibly preventing DNA damage as indicated by blocking the necessitating step of apoptosis following UVB injury.

Effects of the isoflavone 4',5,7-trihydroxyisoflavone (genistein) on psoralen plus ultraviolet A radiation (PUVA)-induced photodamage.

Long-term psoralen plus ultraviolet A radiation (PUVA) therapy is associated with an increased risk of squamous cell carcinoma and malignant melanoma. Genistein (4',5,7-trihydroxyisoflavone), a major isoflavone in soybeans and a specific inhibitor of protein tyrosine kinase, has been shown to inhibit UVB induced skin carcinogenesis in hairless mice. For this study we examined the protective effects of topical genistein on PUVA-induced photodamage. In two separate experiments, genistein in a dimethyl sulfoxide/acetone (1:9) solution was applied to SKH-1 female mice 1 h post 8-methoxy-psoralen dosing and 1 h prior to UVA irradiation. Application of genistein significantly decreased PUVA-induced skin thickening, and greatly diminished cutaneous erythema and ulceration in a dose-dependent manner. Histological examination showed that PUVA treatment of mouse skin induced dramatic inflammatory changes throughout the epidermis; topical genistein prevented these changes without noticeable adverse effects. Cells containing cleaved poly(ADP-ribose) polymerase (PARP) and active caspase-3 were significantly increased in PUVA-treated skin (P < 0.05 and P < 0.0001, respectively) as compared with unexposed control skin. Topical genistein completely inhibited cleavage of PARP and caspase-3. Proliferating cell nuclear antigen (PCNA) positive cells were observed in suprabasal areas of the epidermis and were significantly decreased in PUVA-treated skin compared with both control samples and samples treated with PUVA plus topical genistein (P < 0.005). These results indicate that genistein protects the skin from PUVA-induced photodamage.