Retrospective analysis of alpha-human papillomavirus (HPV) types in tissue samples from anogenital dysplasias - introduction of the RICH (Risk of HPV-related Carcinoma in HIV+/- patients) score.

BACKGROUND: Chronic viral infections caused by highly contagious human papillomaviruses (HPVs) from the alpha genus are a substantial risk factor for tumour diseases. OBJECTIVES: The goal of this study was to compare the HPV infection pattern with histology in a patient group of immunocompromised HIV+ and non-immunocompromised patients with anal intraepithelial neoplasia. MATERIALS AND METHODS: Tissue samples (n = 210) from the anogenital area of 121 patients underwent retrospective histological and molecular examination for HPV DNA prevalence by chip analysis. The study was part of a cancer screening from the Dermatology Department of the LMU Munich, Germany. All data were collected and processed anonymously. RESULTS: HPV 6 or 11 are more abundant in tissue samples from histologically diagnosed condylomata acuminata (47.7%) compared to grade 1, 2, and 3 intraepithelial neoplasias (IN 1-3). Detection of high-risk (hr) alpha-HPV DNA was significantly higher in tissue samples from IN 3 (67.5%) compared to IN 1 and 2 (12.9%), and compared to condylomata acuminata (29.5%). No HPV types were detected in histologically unremarkable tissue samples. There was a significant association between the prevalence of HPV 16 and the classifications IN 1 to IN 3 (χ2 (2) = 13.62, P = 0.001). We identified a significant correlation between the prevalence of high-risk and low-risk (lr) HPV types and HIV, especially mixed infections of different HPV types correlated with high-grade IN. Based on the present data, we suggest the risk of carcinoma in HIV+/- patients (RICH) score and test it in the 121 patients. CONCLUSIONS: hr alpha-HPVs, mainly HPV 16, are associated with increased oncogenic potential of premalignant lesions (IN 1-3), especially in HIV+ patients. Based on the combination of HIV/HPV-testing and histological analysis, we identified correlations that could potentially forecast the risk of malignant transformation and summarized them in the form of RICH score.

The impact of sentinel node dissection on disease-free and overall tumour-specific survival in melanoma patients: a single centre group-matched analysis of 1192 patients.

BACKGROUND: Sentinel lymph node dissection (SLND) is considered a standard staging procedure providing important prognostic information on melanoma patients. It remains a matter of debate, whether SLND and hence, removal of potential lymph node micrometastasis will alter survival outcome. OBJECTIVE: The aim of this group-matched analysis was to compare survival data of a large cohort of melanoma patients who were treated by wide local excision only (WLE) and nodal observation (WLE group) to a group of patients treated with WLE plus SLND group to investigate the potential therapeutic benefit of SLND in the treatment of patients with melanoma. METHODS AND MATERIALS: A total of 596 consecutive patients who had undergone WLE plus SLND between 1996 and 2003 were assessed. As a historical control group 596 patients treated with WLE and nodal observation but without SLND between 1986 and 1995 were selected. The groups were matched according to sex, age, Breslow tumour thickness and localization of primary tumour. The adjuvant treatment and follow-up examinations were performed according to protocols of the German Dermatologic Cooperative Oncology Group (DeCOG) and applicable study protocols that our clinic participated in; and hence, subject to change over time. RESULTS: Kaplan-Meier testing revealed significant differences in survival in favour of the SLND group. Mean overall tumour-specific survival (OS) was 102.7 months in the SLND group vs. 97.0 months in the WLE group respectively (P-value: 0.024). Disease-free survival (log-rank test: 0.003) and time to lymph node progression (P-value: <0.01) also differed significantly between the two groups. CONCLUSION: SLND is not only an important diagnostic procedure, but might also be of therapeutic benefit in terms of disease-free and overall tumour-specific survival of melanoma patients.

[Metal implant sensitivity: clinical and histological presentation]. / Klinik und Histologie Metallimplantat-assoziierter Hauterscheinungen.

Metal implant sensitivity (intolerance) can cause pain, reduced mobility, loosening of the implant and skin rashes. Knowledge of differential diagnoses, histology and appropriate diagnostics are essential for proper diagnosis. To outline typical clinical signs and histology in metal-implant-associated skin lesions we present three exemplary patients from our implant allergy outpatient department and give an overview of the current literature regarding metal implant sensitivity. In patients with a negative patch test the lymphocyte transformation test may reveal metal sensitization. Even "pure" titanium alloys may contain traces of nickel. The histology of implant-associated skin reactions goes from teleangiectatic postimplantation erythema to eczema and vasculitis. Based on the synopsis of history, clinical picture, allergological testing and histology, metal implant sensitivity can be diagnosed more precisely.

The hand eczema proteome: imbalance of epidermal barrier proteins.

BACKGROUND: Chronic hand eczema (CHE) is a common skin disease with a high socioeconomic impact. While some light has been shed on the genetic factors that predispose individuals to the disease, little is known about its actual pathogenesis. OBJECTIVES: We aimed to carry out a systematic and comprehensive analysis of the differential protein expression in CHE using modern mass spectrometry. METHODS: We performed liquid chromatography with tandem mass spectrometry analyses and label-free quantification to analyse the proteomic profile of palmar skin from 12 individuals (six patients with hand eczema and six healthy volunteers). Immunohistochemistry of the palmar skin from seven different patients with hand eczema and seven different healthy volunteers was performed in a second step. RESULTS: With this method we were able to identify 185 candidate proteins with a significantly different abundance in the hand eczema samples. Among them we found several barrier proteins: filaggrin (FLG), FLG-2 and hornerin were all downregulated in the hand eczema samples, as were the desquamation-related enzymes kallikrein-related peptidase (KLK)5 and KLK7 and cystatin E/M. The antimicrobial peptides S100A7 and S100A8/A9 and the small proline-rich protein 2B and S100A11 were upregulated in the diseased skin. Immunohistochemistry confirmed these findings. CONCLUSIONS: Our results corroborate the assumption that skin barrier dysfunction plays an essential role in the pathogenesis of CHE.

Treatment of cutaneous T-cell lymphoma with oral alitretinoin.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a potentially life-limiting malignant disease. Treatment strategies in CTCL aim at disease control and remission with the lowest possible side-effects. OBJECTIVE: Recent reports suggest that the new vitamin A derivative alitretinoin might be a well-tolerated treatment option. METHODS: We analysed the files of 11 CTCL patients with mycosis fungoides (n = 10) or Sézary syndrome (n = 1), who were treated with oral alitretinoin alone or in combination with standard treatment based on individual off-label treatment decisions. Patients had been monitored every 4-8 weeks with skin examination and laboratory analyses. RESULTS: Ten of 11 patients (90.9%) showed a marked improvement of their CTCL skin lesions and no progress of the disease during treatment with alitretinoin, one patient showed no response to the treatment (9.1%). Four of the responding patients (40.0%) had a complete response and 6 (60.0%) had a partial response. Average time to response was 2.5 months. Duration of treatment varied depending on whether patients had reached complete or partial remission. In general, alitretinoin was well tolerated. One of 11 patients developed high non-fasting average serum cholesterol (>300 mg/dL) and 1/11 a mean non-fasting triglyceride value >500 mg/dL. In 3/11 patients, thyroid-stimulating hormone declined without clinical symptoms during treatment, with one of the patients also showing a decreased thyroxin level. CONCLUSION: In our group of CTCL patients we noticed a low rate of side-effects and an overall good clinical response to treatment with alitretinoin. Further studies are required to substantiate this early clinical observation.

High-definition optical coherence tomography and reflectance confocal microscopy in the in vivo visualization of a reaction to permanent make-up.

BACKGROUND AND OBJECTIVES: After permanent make-up treatments, eczematous and granulomatous reactions may occur which need anti-inflammatory treatment. For the definite diagnosis oftentimes biopsies are recommended. In vivo imaging such as reflectance confocal microscopy (RCM) and high-definition optical coherence tomography (HD-OCT) has been successfully used in the non-invasive diagnosis of various dermatoses before. METHODS: Here, we report on non-invasive imaging of a reaction towards permanent make-up in a 40-year-old woman by using HD-OCT and RCM. RESULTS: Both in HD-OCT and in RCM subepidermal pigment and granulomatous changes could be visualized and correlated with the histopathological findings. Regression of the lesions in response to topical steroids and intralesional injections of steroids and 5-fluorouracil is reported and treatment options are discussed. CONCLUSION: Non-invasive imaging techniques such as HD-OCT and RCM allow the visualization and localization of exogenous pigment and help in the evaluation of adverse reactions due to permanent make-up tattooing.

[Massive granuloma formation after long-term use of dermal fillers]. / Ausgeprägte Granulombildung nach langjähriger dermaler Fillerinjektion.

BACKGROUND: Since dermal fillers were introduced in 1981, millions of patients have undergone wrinkle treatment with dermal fillers. Except for autologous fat, all fillers can act as potential foreign bodies, which have the potential ability to induce an immune reaction. Persisting material may induce activation of the immune system and finally granuloma formation. Frequency, histology, and clinical presentation of such foreign body reactions may vary depending on the filler used. CASE REPORT: This case describes a patient who received innumerable filler injections over the last two decades presenting with massive facial granulomas.

Predictors of clinical effectiveness of Hymenoptera venom immunotherapy.

BACKGROUND: Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown. OBJECTIVE: Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC). METHODS: In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC > 20.0 µg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models. RESULTS: Ninety-eight patients (6.4%) presented with MIS and/or BTC > 20.0 µg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 µg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P < 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P < 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P < 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate. CONCLUSION: The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC > 20 µg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

[Recurrent fibrosarcomatous dermatofibrosarcoma protuberans. Ultrasound imaging]. / Rezidiv eines fibrosarkomatösen Dermatofibrosarcoma protuberans. Sonographische Darstellung.

Dermatofibrosarcoma protuberans (DFSP) is a rare dermal tumor of intermediate malignancy with a locally aggressive growth behavior with a high rate of recurrence. Wide local excision with histographic margin control as well as regular follow-ups including clinical as well as ultrasound examination are crucial to detect local recurrence or metastasis. Ultrasound imaging can not only identify recurrences but also asses their extent. We report on a patient with a relapse of fibrosarcomatous DFSP, which could be demonstrated by ultrasound imaging.

Drug-induced Sweet's syndrome after mitoxantrone therapy in a patient with multiple sclerosis.

We report a 55-year-old male patient with secondary progressive multiple sclerosis who developed an acute febrile syndrome with fever, neutrophilia and tender erythematous plaques and papules on his upper extremities after his fifth mitoxantrone infusion. Infectious, haematological and rheumatological diseases were ruled out, but skin biopsy showed neutrophilic infiltrations in the dermis consistent with Sweet's syndrome. Treatment with oral corticosteroids led to prompt improvement of systemic and cutaneous symptoms. To our knowledge, this is the first report of a patient with Sweet's syndrome after mitoxantrone therapy. Clinicians should be aware of Sweet's syndrome in patients with otherwise unexplained acute febrile illness and erythematous skin rash in association with mitoxantrone therapy. Skin biopsy helped to exclude other diseases and confirmed Sweet's syndrome.

[Verrucous squamous cell carcinoma complicating hypertrophic lichen planus. Three case reports and review of the literature]. / Verruköses spinozelluläres Karzinom auf Lichen ruber hypertrophicus. Drei Fallberichte mit Literaturüberblick.

Lichen planus is a chronic mucocutaneous T-cell-mediated disease, whose cause is still unknown. The first case of lichen planus that transformed into squamous cell carcinoma was reported in 1903. We present three patients in whom squamous cell carcinomas were identified in chronic lichen planus. The world literature includes at least 91 cases, including our three cases. In an epidemiological study, no significant risk of transformation of cutaneous lichen planus into squamous cell carcinomas was found. In contrast, there is a significantly higher risk of malignant transformation in mucosal lichen planus, so that the WHO had graded mucosal lichen planus as a premalignant condition.

Detection of Merkel cell polyomavirus DNA in atypical fibroxanthoma in correlation to clinical features.

A clear etiopathogenetic concept for atypical fibroxanthoma (AFX) is not established yet. Nevertheless, AFX is known as a pleomorphic but indolent tumor primarily of the elderly and/or immunosuppressed patient occurring in severely sun- or radiation-damaged skin. These risk factors are almost identical to those of Merkel cell carcinoma (MCC), a highly malignant skin tumor being thought to be pathogenetically associated with the recently discovered Merkel cell polyomavirus (MCPyV). Because AFX and MCC share risk factors, the aim of this study was to evaluate presence of MCPyV DNA in 23 cases of AFX by PCR and direct DNA sequencing. Subsequently, we correlated clinical features with MCPyV DNA status in AFX. We detected MCPyV DNA in 4 of 23 AFX. All patients with MCPyV DNA-positive tumors were men. The mean age of patients with MCPyV DNA-positive AFX was 84.8 ± 8.7 years (vs. 75.2 ± 7.8 years of MCPyV DNA-negative AFX), the mean duration of tumor growth was 4.5 ± 2.3 months (vs. 5.1 ± 2.8 months) and the mean tumor diameter was 1.2 ± 0.3 cm (vs. 1.3 ± 0.7 cm). Ulceration was present in 75% of MCPyV DNA-positive tumors (vs. 65.2%). In conclusion, MCPyV DNA is present in 17% of AFX, in this cohort affecting predominantly male patients with higher age (>80 years). Clinical features seem to be independent of MCPyV DNA status. Although the role of MCPyV is unclear in this setting, it may act as a cofactor in the tumorigenesis of AFX in a subset of cases.

[Sjögren-associated MALT-type lymphoma of labial salivary glands: rare constellation with amyloidosis and IgM-paraproteinemia]. / Sjögren-assoziiertes MALT-Lymphom der Lippenspeicheldrüsen: Seltene Konstellation mit Amyloidbildung und IgM-Paraproteinämie.

We report a complex and rare combination of clinical and histological findings in a 59-year-old female patient: severe sicca-syndrome due to M. Sjögren, marginal zone B-cell lymphoma (MALT-type) in labial salivary glands with localized amyloid deposition, IgM-paraproteinemia, and Bence-Jones proteinuria. The causal association of these findings could only be elucidated by intense interdisciplinary correlation of all findings.

High probability of comorbidities in bronchial asthma in Germany.

Clinical experience has shown that allergic and non-allergic respiratory, metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial asthma. However, no study has been carried out that calculates the chance of manifestation of these disorders with bronchial asthma in Saarland and Rhineland-Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the present study systematically analyzed the co-prevalence and odds ratios of comorbidities in the asthma population in Germany. The odds ratios were adjusted for age and sex for all comorbidities for patients with asthma vs. without asthma. Bronchial asthma was strongly associated with allergic and with a lesser extent to non-allergic comorbidities: OR 7.02 (95%CI:6.83-7.22) for allergic rhinitis; OR 4.98 (95%CI:4.67-5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33-2.52) atopic dermatitis; OR 2.47 (95%CI:2.16-2.82) food allergy, and OR 1.69 (95%CI:1.61-1.78) drug allergy. Interestingly, increased ORs were found for respiratory diseases: 2.06 (95%CI:1.64-2.58) vocal dysfunction; 1.83 (95%CI:1.74-1.92) pneumonia; 1.78 (95%CI:1.73-1.84) sinusitis; 1.71 (95%CI:1.65-1.78) rhinopharyngitis; 2.55 (95%CI:2.03-3.19) obstructive sleep apnea; 1.42 (95%CI:1.25-1.61) pulmonary embolism, and 3.75 (95%CI:1.64-8.53) bronchopulmonary aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79-0.94) did not coexist with asthma. Based on the calculated chances of manifestation for these comorbidities, especially allergic and respiratory, to a lesser extent also metabolic, cardiovascular, and mental disorders should be taken into consideration in the diagnostic and treatment strategy of bronchial asthma. BRONCHIAL ASTHMA: PREVALENCE OF CO-EXISTING DISEASES IN GERMANY: Patients in Germany with bronchial asthma are highly likely to suffer from co-existing diseases and their treatments should reflect this. Quoc Thai Dinh at Saarland University Hospital in Homburg, Germany, and co-workers conducted a large-scale study of patients presenting with bronchial asthma in the Saarland region between 2009 and 2012. Patients with asthma made up 5.4% of the region's total population, with a higher prevalence occurring in females. They found that bronchial asthma was strongly associated with allergic comorbidities such as rhinitis. Indeed, asthmatic patients had a seven times higher chance to suffer from allergic rhinitis than the rest of the population, and were at higher risk of respiratory diseases like pneumonia and obstructive sleep apnea syndrome. Further associations included cardiovascular, metabolic and mental disorders. Dinh's team call for asthma treatments to take such comorbidities into account.