Clinical assessment of skin phototypes: watch your words!

Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardised way. This can have implications on the results of relevant dermato-epidemiological studies. To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment. Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country. Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender. The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies.

Gianotti-Crosti syndrome associated with Ebstein-Barr virus and Parvovirus B-19 coinfection in a male adult: case report and review of the literature.

Gianotti-Crosti syndrome (GCS) is a self-limiting, mostly childhood-appearing, cutaneous eruption with characteristic symmetric areal distribution. The original cases, described by Gianotti in 1955, were associated with hepatitis B virus infection, but other viral and bacterial infections, as well as immunizations, have been implied in etiology of this condition. Adult cases are rare and have been reported almost exclusively in women. We present the case of a 20-year-old Caucasian man who had typical clinical presentation: monomorphic pale, pink-to-flesh - colored or erythematous papules and papulovesicles localized symmetrically over the extensor surfaces of the extremities, buttocks and the face; some lesions were detected on knees, elbows and palms, as well. Laboratory tests revealed slight bilirubin and alanine aminotransaminase elevation. Serology tests demonstrated antibodies against Epstein-Barr virus and parvovirus B-19. Histology of skin biopsy specimens revealed a vesicular dermatitis with perivascular lymphocytic infiltrate. Oral and topical corticosteroids and oral antihistamines led to complete resolution of lesions in 3 weeks. GCS is rare in adults, especially men. To the best of our knowledge, this is the fifth male adult case and the first with Parvovirus B-19 and EBV coinfection.

Laugier-Hunziker syndrome--Case report.

Laugier-Hunziker syndrome is a rare, acquired disorder characterized by lenticular hyperpigmentation of the oral mucosa and longitudinal melanonychia. We present the case of a 63-year-old female with progressive, asymptomatic hyperpigmentation of buccal mucosa and a 7-year history of hyperpigmentation in several fingernails. Laugier-Hunziker syndrome was diagnosed based on the clinical features presented, dermoscopic findings and exclusion of underlying systemic diseases. Laugier-Hunziker syndrome is regarded as a diagnosis of exclusion. By identifying Laugier-Hunziker syndrome, other, more severe syndromes associated with hyperpigmentations can be excluded, namely Addison's disease and Peutz-Jeghers syndrome.

Laugier-Hunziker syndrome - Case report

Laugier-Hunziker syndrome is a rare, acquired disorder characterized by lenticular hyperpigmentation of the oral mucosa and longitudinal melanonychia. We present the case of a 63-year-old female with progressive, asymptomatic hyperpigmentation of buccal mucosa and a 7-year history of hyperpigmentation in several fingernails. Laugier-Hunziker syndrome was diagnosed based on the clinical features presented, dermoscopic findings and exclusion of underlying systemic diseases. Laugier-Hunziker syndrome is regarded as a diagnosis of exclusion. By identifying Laugier-Hunziker syndrome, other, more severe syndromes associated with hyperpigmentations can be excluded, namely Addison’s disease and Peutz-Jeghers syndrome.

TNF, IL12B, and IFNG Gene Polymorphisms in Serbian Patients with Psoriasis.

BACKGROUND: Psoriasis is a common chronic inflammatory skin disease with a strong genetic basis. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) such are IL-12 and IL-23, and interferon gamma (IFN-γ) are released from various inflammatory and resident cells, and have been implicated in the initiation/maintenance of inflammation. Certain alleles of the aforementioned cytokines may be associated with disease susceptibility/severity. OBJECTIVE: To investigate the association of three common functional gene polymorphisms, namely TNF -308 G/A (rs1800629), IL12B (encoding the p40 subunit of IL-12/23) +1188 A/C (rs3212227), and IFNG +874 T/A (rs2430561) with psoriasis development and severity in Serbian patients. METHODS: We genotyped 130 patients with psoriasis (26 of whom also had psoriatic arthritis) and 259 controls; rs1800629 and rs3212227, and rs2430561, by real-time PCR assay. RESULTS: The TNF GG genotype was detected at a higher frequency in patients with psoriasis compared to control subjects (OR, 1.420; 95% CI, 0.870~2.403) without statistical significance (p=0.191). Lack of the TNF G allele was associated with lower psoriasis severity (p=0.007). The IL12B AC genotype was underrepresented in the patients with psoriatic arthritis compared to healthy subjects (OR, 0.308; 95% CI, 0.090~1.057; p=0.049). The distribution of the rs2430561 allele and genotype frequencies was similar between patients with psoriasis and controls. CONCLUSION: Our study demonstrates an effect of the rs1800629 on psoriasis severity, and a marginal impact of the rs3212227 on susceptibility to psoriatic arthritis. Collectively, our results obtained in a Serbian cohort expand current knowledge regarding individual predisposition to psoriatic disease.

Novel and recurrent FERMT1 gene mutations in Kindler syndrome.

Kindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic inflammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fermitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phenotype correlation in this disorder.

[Dermatomyositis associated with metastatic rectal adenocarcinoma: case report].

INTRODUCTION: Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous changes. The disease belongs to paraneoplastic dermatosis. Association of dermatomyositis with malignant conditions has been described in various studies. We present a patient with paraneoplastic dermatomyositis associated with metastatic rectal adenocarcinoma. CASE REPORT: A 66-year-old man was hospitalized in our Institute due to skin changes and myopathy in October 2006. According to the medical documents and history, he underwent surgery because of rectal adenocarcinoma in April 2006. Skin changes appeared 5 months before, while aggravation occurred 6 months after the surgery. The diagnosis of dermatomyositis was based on: characteristic clinical picture; the elevated serum level of following enzymes: creatinine kinase, lactate dehydrogenase; the presence of anti-Mi 2 antibodies in serum; electromyographic finding; and by histology of the muscle biopsy. Paraneoplastic nature of dermatomyositis was confirmed by computer tomography of the abdomen which revealed multiple deposits in the liver, by explorative laparotomy showing peritoneal dissemination and histopathological analysis that verified metastatic adenocarcinoma of the rectum. The oncological consulting team suggested chemotherapy which was not carried out because of the rapid lethal outcome. CONCLUSION: We report a case of paraneoplastic dermatomyositis associated with metastatic rectal adenocarcinoma and lethal outcome, and suggest a comprehensive evaluation of patients with dermatomyositis older than 50 years in order to exclude or verify the occult malignancy.

Granulomatous rosacea-like leukemid in a patient with acute myeloid leukemia.

INTRODUCTION: Skin findings in leukemias may be divided into specific lesions (leukemia cutis) and non-specific lesions (leukemids) which may be found in up to 80% of all patients with leukemias. The leukemids vary clinically and they are usually a manifestation of bone marrow or immunologic impairment, but also Sweet syndrome, pyoderma gangrenosum, erythroderma, maculopapular exanthema, prurigo-like papules, generalized pigmentation, follicular mucinosis, generalized pruritus may be found during the course of leukemia. CASE REPORT: We report a 70-year-old male with a 3-month history of erythema, papules and pustules on the face, ears and neck and over a month history of refractory anemia, anorexia, weight loss, malaise, and fever. Physical examination revealed symmetric erythematous, violaceous papules, papulo-nodules and plaques with slate scale and sparse, small pustules on the face, earlobes and neck. Histopathologic findings of involved skin showed diffuse mixed inflammatory cell infiltrate with perifollicular accentuation and focal granulomatous inflammation in the papillary and upper reticular dermis. Extensive checkup revealed the presence of acute myeloid leukemia French-American-British (FAB) classification subtype M2, with signs of three-lineage dysplasia. The patient was treated by L6 protocol which led to complete remission, both in bone marrow and skin, but after seven months he had relapse of leukemia with the fatal outcome. CONCLUSION: This case indicates the importance of skin eruptions in the context of hematological malignancies.

Cytokine concentrations in basal cell carcinomas of different histological types and localization.

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignant skin tumor. Cytokines as major mediators of the immune system have been shown to play an important role in biology of the neoplasm with the general predomination of Th2 cytokines, whereas IFN-? and other Th1 cytokines are prevalent in spontaneously regressing tumors. OBJECTIVE: We were interested in comparing cytokine levels in BCC and cutaneous squamous cell tumors with BCC of different localization and histological subtypes. MATERIAL AND METHODS: Explants from freshly excised BCC from 18 patients, and cutaneous squamous cell tumors (solar keratoses and Bowen's disease) from 9 patients were cultivated for 24 h. Cytokine (IL- 2, IFN-gamma, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNFalpha, IL-1beta) concentrations in culture supernatants were determined by a sandwich immunoassay. RESULTS: Tissue explants of BCC contained significantly higher concentrations of IL-1beta, IL-4, IL-5, and IL-6 compared to those of squamous cell tumors. Higher levels of TNF-alpha (p = 0.042), IL-4 (p = 0.028), and IL-5 (p = 0.012) were found in tumors localized to the head and neck compared to those on the trunk or extremities. Interleukin-6 concentrations were higher in aggressive BCC variants (infiltrative and micronodular), but the difference was not statistically significant (p = 0.068). CONCLUSIONS: Confirming the earlier findings that BCC is a tumor with a Th2 cytokine microenvironment, this study further shows that BCC situated on the head and neck produce even more of certain Th2 cytokines (IL-4 and IL-5) and TNF-alpha, a crucial immunosuppressive cytokine released upon UVB irradiation.

Acrokeratosis paraneoplastica Bazex syndrome associated with esophageal squamocellular carcinoma.

BACKGROUND: Acrokeratosis paraneoplastica Bazex (APB) is a very rare disease in the group of obligate paraneoplastic dermatoses, associated mostly with squamous cell carcinoma of the upper aerodigestive tract and metastatic cervical lymphadenopathy. The disease is characterized by violaceous erythemosquamous changes on the acral regions. This entity was first reported by Bazex in 1965. About 160 cases have been presented so far. CASE REPORT: We presented a patient with a three-month history of violaceous erythema, edema, erosions and scaling on the acral regions, elbows and knees and severe nail dystrophy. When the diagnosis was established, he did not have any symptom of internal malignancy. Esophagogastroscopy revealed ulcerovegetant lesion of the esophagus, while histology showed squamocellular invasive carcinoma. Surgical tumor removal resulted in significant improvement of skin changes in 15 days. Unfortunately, four months later, extensive skin lesions pointed to metastasis of squamous cell carcinoma. CONCLUSION: Skin changes can precede a few years the first manifestations of neoplasia. The course of the disease in our patient proved that APB is a specific marker of underlying malignancy.

Recessive dystrophic epidermolysis bullosa: presentation of two forms.

Dystrophic epidermolysis bullosa (DEB) and aplasia cutis congenita (ACC), also known as congenital localized absence of skin (CLAS) are rare clinical entities. Aplasia cutis congenita presented in conjunction with simplex, junctional, or dystrophic types of epidermolysis bullosa (EB) is classified as type-6 ACC. This association was initially described and referred in the literature as Bart syndrome. We describe two cases of recessive DEB (RDEB), one with the major Hallopeau-Siemens (RDEB-HS) subtype and one case with the minor RDEB inversa (RDEB-I) subtype associated with ACC localized on the lower extremities. Full clinical history and transmission electron microscopic findings are presented for both cases. To date, only five cases of RDEB presenting with ACC have been reported in the literature. Detailed descriptions of the association of RDEB and ACC in the literature are scarce. It seems that this condition is probably more common in clinical practice than described in the literature. Our findings confirm that the term, Bart syndrome, should not be considered as a separate entity or clinical variant of dominant dystrophic EB as it was initially described. Congenital localized absence of skin may be associated with any of the three major types of EB (simplex, junctional, or dystrophic).

Systemic retinoids in chemoprevention of non-melanoma skin cancer.

BACKGROUND: The incidence of non-melanoma skin cancer is increasing worldwide. Systemic retinoids are useful for the chemoprophylaxis of non-melanoma skin cancers. Retinoids have pleiotropic effects, but their exact cancer chemopreventive mechanism is still not clear. OBJECTIVE: The aim of this study was to review published literature evaluating the use of oral retinoids in the chemoprevention of non-melanoma skin cancers. METHODS: The study reviewed all relevant papers found through a search of the electronic databases MEDLINE (from 1966 to January 2008) and Embase (from 1974 to January 2008). RESULTS/CONCLUSION: General and specific indications for retinoid chemoprophylaxis are defined. The pharmacokinetics and dose regimens of the two most commonly used oral retinoids (isotretinoin and acitretin) in the chemoprevention of non-melanoma skin cancers are presented. The use of oral retinoids is associated with adverse effects, which are discussed in detail. The future of retinoid cancer chemoprevention depends on the development and research of novel retinoids with improved bioavailability and minimized toxicity.

Pagetoid reticulosis of Woringer-Kolopp.

Pagetoid reticulosis of Woringer-Kolopp is a rare form of cutaneous T-cell lymphoma that primarily affects middle-aged males. It is characterized by the presence of one or several scaly patches and plaques with an acral distribution. We present a case of a 58-year-old woman, otherwise healthy, with a 5-month history of asymptomatic, hyperkeratotic plaques on the hands and feet. Histological and immunohistochemical analysis confirmed the diagnosis. Nearly complete spontaneous regression was noted 7 months after the initial examination. After 5 years no evidence of the disease remained.

Atypical pyoderma gangrenosum in a patient with osteomyelofibrosis.

BACKGROUND: Atypical forms of pyoderma gangrenosum generally appear on the upper extremities; most frequently they are associated with myeloproliferative disorders, including osteomyelofibrosis. A response to systemic steroids is more pronounced than in classical form. Sometimes it may be the first sign of an underlying malignancy. CASE REPORT: We reported a patient with atypical pyoderma gangrenosum developed during the course of a myeloid malignancy--osteomyelofibrosis. The lesions occurred after a minor trauma. Painful blistering plaques, with an elevated, bluish-gray border were located on the dorsal aspect of hands. No skin malignancy was found. The lesions resolved rapidly to systemic steroids. CONCLUSION: Considering the unusual clinical presentation which makes the diagnosis difficult, as well as the fact that atypical forms of pyoderma gangrenosum can be the first sign of malignancies, especially myeloproliferative ones, recognizing this entity enables timely guiding future investigations toward their prompt detection.

Surgical management of squamous cell carcinoma of the lip: analysis of a 10-year experience in 223 patients.

BACKGROUND: The most common type of lip carcinoma is squamous cell carcinoma (SCC), accounting for approximately 90% of all oral malignancies. Currently, surgery and/or radiotherapy are considered the standards of care for SCC of the lip. MATERIALS AND METHODS: We retrospectively analyzed medical records of patients diagnosed with SCC of the lip at the Clinic for Maxillofacial surgery at University of Belgrade (Belgrade, Serbia) during a period between 1991 and 2000. RESULTS: A total of 223 patients with SCC of the lip were diagnosed and treated during a 10-year period. The overall male-to-female ratio was 5 to 0. The most frequently affected site was the lower lip (92.8%). Mean diameter of the tumor was 30.1 mm (range, 5 to 80 mm). Neck lymph node metastases at presentation was detected in 26.5% of patients, who subsequently underwent neck dissection. We observed a linear trend in the association between the size of the tumor and the clinical stage of the neck (chi2 = 15.1; df = 1; P < .0001). Different surgical techniques were used for reconstruction of the lip defect after tumor removal. After a median follow-up of 56 months (range, 15 to 78 months), local recurrence occurred in 10.8% of patients while regional metastases developed in 4.5% of patients. Mortality from SCC of the lip was only 2.2%. CONCLUSION: SCC of the lip generally has a favorable outcome. Recently, there have been no major advances in lip reconstruction but rather continued improvement on accepted techniques. Early detection is essential for the successful treatment of SCC of the lip, which requires a multidisciplinary approach.

[Primary systemic amyloidosis].

BACKGROUND: Systemic amyloidosis is a rare disorder which usually occurs in aged persons and has a poor prognosis. Systemic amyloidosis can be primary, occasionally associated with multiple myeloma, or secondary, associated with another disease. CASE REPORT: We presented a 72-year-old male patient with periocular purpura ("racoon sign") and waxy papules, petechiae and ecchymoses on the neck and thoracic area. Purpuric macules were present also on the lips and tongue which was edematous (macroglossia). The skin lesions occurred two years earlier, the patient lost more than 15 kilograms of the body mass for less than a year. Immunoelectrophoresis of urine and serum demonstrated the presence of immunoglobulin light chains of the circulating monoclonal protein. Histopathological examination of skin lesions showed Congo red positive deposits in the derm. Cardiac evaluation revealed the signs of heart failure, and renal evaluation revealed nephrotic syndrome, with excessive protein lost. He was treated with oral melphalan and prednisolone, and died 7 days after starting the therapy due to heart failure. CONCLUSION: This patient considered as a rare case with systemic amyloidosis highlights the importance of histopathological and physical examination in any cases with periocular purpura, petechiae, ecchymoses and macroglossia.