[Hidradenitis suppurativa]. / Hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin and systemic disease that is associated with considerable discomfort and a significant reduction in the quality of life. Despite a significantly increased understanding of the disease, the diagnosis is still delayed for many years. Delayed patient access to suitable treatment often leads to disease progression with increased surgical interventions and the occurrence of possible comorbidities. In recent years, there has been an improved understanding of the pathophysiology and, as a result the authorization of modern therapeutic agents for HS. The treatment of HS is based on three treatment pillars: surgery, antibiotics and biologics. Additionally, risk factors, such as smoking and obesity should be positively influenced. Knowledge of comorbidities and their interdisciplinary treatment is important for the individualized care of patients.

[Cutaneous squamous cell carcinoma]. / Kutanes Plattenepithelkarzinom.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers of the Caucasian population and accounts for 20% of all skin tumours. An S3 guideline of the German Guideline Program in Oncology has been available since 2019. The diagnosis is based on the clinical examination. Excision and histological confirmation is required for all clinically suspicious lesions to allow prognostic assessment and correct treatment. The therapy of first choice is complete excision with histological control of the surgical margin. In cSCC with risk factors such as tumor thickness >6 mm, sentinel lymph node biopsy may be discussed, but there is currently no clear evidence of its prognostic and therapeutic relevance. Adjuvant radiation therapy may be considered in cases of high risk of recurrence and should be tested in cases of inoperable tumors. The indication for electrochemotherapy should also be considered in the treatment of local or locoregional recurrence. The immune checkpoint inhibitor cemiplimab is approved for the treatment of inoperable or metastasized cSCC. In case of contraindications, chemotherapeutic agents, epidermal growth factor receptor (EGFR) inhibitors or palliative radiotherapy can be used. Since the evidence is low in these cases, a systemic therapy should be used preferentially within clinical studies. Follow-up care should be risk-adapted and includes a dermatological control, supplemented by ultrasound examinations in high-risk patients.

[Cutaneous squamous cell carcinoma]. / Kutanes Plattenepithelkarzinom.

Squamous cell carcinoma (SCC) of the skin accounts for 20 % of non-melanoma skin cancer and is one of the most frequent types of cancer in Caucasian populations. Diagnosis is based on the clinical features and should be histopathologically confirmed to adequately address the prognosis and treatment. Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary SCC. Sentinel lymph node biopsies (SLNB) can be considered in SCC with a tumor thickness of >6 mm but there is currently no evidence concerning prognostic and therapeutic effects. Radiotherapy can be discussed as an alternative to surgery for inoperable tumors or as adjuvant therapy for a high risk of recurrence. In SCC with distant metastases various chemotherapeutic agents are used; however, there is no standard regimen. The epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint blockers can be discussed as treatment options, preferentially in clinical trials. There is no standard follow-up schedule for patients with SCC. A risk-adapted follow-up is recommended based on the risk of metastatic spread or development of new lesions primarily by dermatological control and supplemented by ultrasound investigations in high risk patients.

[Cutaneous squamous cell carcinoma: a review with consideration of special patient groups]. / Kutanes Plattenepithelkarzinom unter Berücksichtigung besonderer Patientengruppen.

The incidence of non-melanoma skin cancer (NMSC) is increasing. Squamous cell carcinoma of the skin (SCC) is a tumor of the elderly. Due to the increasing life expectancy, SCC will become more and more frequent in the future. Generally SCC has a favorable prognosis. Standard therapy is microscopically- controlled excision. Therapy of advanced and metastatic SCC is still challenging. Patients with regional lymph node metastasis have ten-year survival rates less than 20%; patients with distant metastases less than 10%. Immunosuppression has been shown to be one of the key prognostic factors for metastasis. The article reviews SCC and focusses on patients being at risk for an unfavorable course.

Treatment of advanced cutaneous squamous cell carcinomas with epidermal growth factor receptor inhibitors.

In advanced cutaneous squamous cell carcinoma (cSCC), efficient medical treatment options are limited in case surgery and radiotherapy failed, particularly since most patients are of higher age and suffer from comorbidities. In many tumor entities, the epidermal growth factor receptor (EGFR) has been established as an important therapeutic target, and blockade of EGFR signaling by monoclonal antibodies or small molecules achieves a therapeutic benefit. EGFR expression is also often dysregulated in cSCC. We report here two patients with advanced cSCC treated with the EGFR inhibitor cetuximab and summarize the current published experience with the use of EGFR inhibitors in cSCC.

[Squamous cell carcinoma developing in oral lichen planus]. / Plattenepithelkarzinom auf dem Boden eines Lichen ruber mucosae.

Oral lichen planus is a mucosal inflammatory disease whose pathogenesis is unclear. The chronic inflammation leads to development of a squamous cell carcinoma in 1-2% of the patients; we present an exemplary case.

VMAT1 deletion causes neuronal loss in the hippocampus and neurocognitive deficits in spatial discrimination.

Vesicular monoamine transporters (VMAT) are involved in presynaptic storage and release of neurotransmitters. While it was thought initially that only VMAT2 is brain expressed and VMAT1 is present only in the periphery, recent data have challenged the exclusive expression of VMAT2 in the brain. To further elucidate the role of VMAT1 brain expression and its potential role in neuropsychiatric disorders, we have investigated mice lacking VMAT1. Comparison of wildtype and knock-out (KO) mice using qPCR and immunohistochemistry documents the expression of VMAT1 in the brain. Deletion of VMAT1 leads to increased hippocampal apoptosis and reduced neurogenesis as assessed by caspase-3-labeling and 5-bromo-deoxy-uridine-labeling. Behavioral data show that mice lacking VMAT1 have neurocognitive deficits. VMAT2 expression is not altered in VMAT1 KO mice, suggesting a distinct role of VMAT1. Our data support VMAT1 brain expression and suggest that VMAT1 plays a key role in survival of hippocampal neurons and thus might contribute to neurocognitive deficits observed in neuropsychiatric disorders.

[Remission of an iatrogenic Kaposi sarcoma in a patient with myasthenia gravis after switching immunosuppressive therapy to the mTOR inhibitor everolimus]. / Remission eines iatrogenen Kaposi-Sarkoms bei Myasthenia gravis nach Umstellung der Immunsuppression auf den mTOR-Inhibitor Everolimus.

Iatrogenic Kaposi sarcomas (KS) in organ transplant recipients are often treated by switching immunosuppressive therapy to an mTOR inhibitor, such as sirolimus or everolimus, as these have immunosuppressive as well as anti-tumor effects. We report on an 80-year-old male patient who developed a disseminated cutaneous KS during therapy with prednisone and azathioprine for myasthenia gravis. After discontinuation of azathioprine therapy and despite continuing therapy with cortisone, the KS progressed and autoantibody levels against the nicotinic acetylcholine receptor increased. During the administration of everolimus, a long-term near-complete remission of KS and a decrease in autoantibodies took place. This case study illustrates that even in non-organ transplant patients with iatrogenic KS, switching to immunosuppressive therapy using an mTOR inhibitor can be beneficial.

[Cutaneous side effects of medical tumor therapy]. / Kutane Nebenwirkungen der medikamentösen Tumortherapie.

Agents used in medical tumor therapies can cause peculiar cutaneous side effects. In particular the newly developed targeted therapies are associated with specific cutaneous side effects, such as a papulopustular exanthems associated with EGFR inhibitors and epithelial skin cancers associated with inhibitors of mutated BRAF. In this review the clinical pictures as well as pathogenetic and therapeutic aspects of the hand-foot-syndrome, papulopustular exanthems, epithelial skin cancers, paronychia and changes of hair and nails as side effects of medical tumor therapies are summarized. Knowledge of these side effects is important to avoid interruption or termination of the tumor therapy, in particular since some of the cutaneous reactions have been shown to correlate with the therapeutic benefit of the tumor therapy.

[Successful treatment of pemphigus foliaceus with rituximab. Report of 3 cases]. / Erfolgreiche Therapie des Pemphigus foliaceus mit Rituximab. Bericht über 3 Patienten.

Treatment of autoimmune bullous diseases, especially of the pemphigus diseases, regularly requires the use of immunosuppressive drugs, often with insufficient clinical benefit but considerable side effects. A variety of autoimmune diseases (such as rheumatoid arthritis, lupus erythematosus, pemphigus vulgaris) have been successfully treated with rituximab, a chimeric monoclonal antibody against CD20, leading to a transient depletion of B cells. We report on three patients with pemphigus foliaceus who responded to rituximab after failing multiple other immunosuppressive therapies. We also examine the controversial issue of continuation therapy with rituximab in detail.

Prevalence and screening costs of hepatitis C virus among Ugandan blood donors.

BACKGROUND: Screening donated blood for hepatitis C virus (HCV) is important for HCV prevention and is routinely practiced in North America and Europe. However, in many African countries little is known about HCV prevalence or cost-effectiveness of HCV antibody (anti-HCV) screening. METHODS: We investigated 2592 plasma specimens collected consecutively from blood donors in central Uganda in 1999. Routine screening by the blood bank included human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and syphilis. To assess HCV prevalence and cost-effectiveness of testing, specimens were additionally tested for anti-HCV IgG by enzyme immunosorbent assay (EIA). Specimens repeatedly reactive (RR) on EIA were tested with a recombinant immunoblot assay (RIBA). RESULTS: Overall, 107 (4.1%) specimens were HCV EIA RR. Fifteen EIA RR specimens (0.6%, 95% confidence interval = 0.3-0.9%) were RIBA positive and 47 (1.8%) were RIBA indeterminate. Most (80%) RIBA-positive specimens were non-reactive for HIV, HBsAg, and syphilis. RIBA positivity was not associated with donor age, sex, number of donations, HIV, or HBsAg positivity. Costs of screening donors for anti-HCV by using EIA were estimated at US Dollars 782 per potential transfusion-associated HCV infection (exposure to RIBA-positive blood) averted. CONCLUSIONS: Current screening tests for other infections are ineffective in removing HCV-positive donations. Testing costs are considerable; cost-effectiveness of identifying HCV-infected donors will be critical in decision making about HCV screening in Uganda.

Hepatitis B vaccination rate of homeless children in Baltimore.

OBJECTIVE: To investigate the hepatitis B vaccination rate in homeless children 2 to 18 years old living in Baltimore City. METHODS: During a 21-month period, 250 children from homeless shelters were enrolled. RESULTS: The percent of children who had received 3 or more doses of hepatitis B vaccine was inversely related to age; 90% in 2- to 5-year-olds and 29% in 13- to 18-year-olds (P<0.0001). Seventy percent of 2- to 5-year-olds had at least some of their vaccine history recorded in the Baltimore Immunization Registry Program but the history was complete in only half. Forty-two percent of 13- to 18-year-olds had no hepatitis B vaccine doses recorded in any source; 49 per cent of 10- to 18-year-olds were either not immunized or had received only one hepatitis B vaccine dose. CONCLUSIONS: Hepatitis B vaccine coverage is high in homeless children up to 9 years of age, whereas the majority of homeless children 10 years of age and older are unprotected against hepatitis B virus infection. Tracking the vaccine records in homeless children is labor intensive. Better public health strategies to deliver hepatitis B vaccine to older homeless children are urgently needed.

Risk factors for HCV infection among blood donors confirmed to be positive for the presence of HCV RNA and not reactive for the presence of anti-HCV.

BACKGROUND: In 1999, NAT of blood donations was implemented to detect "window-period" infections. Blood donors who have confirmed NAT results positive for the presence of HCV in the absence of anti-HCV are likely to have been recently infected. Of over 26.8 million donations tested between March 3, 1999, and March 31, 2003, 810 were HCV-reactive by NAT. A subset of these donors was assessed for recent exposure risk. STUDY DESIGN AND METHODS: All anti-HCV- blood donors with reactive, unconfirmed HCV NAT results were invited to participate in a study that included an extensive demographic and risk questionnaire. Confirmed HCV+ cases were compared to HCV- (falsely positive) controls for histories of potential risk factors during the 6 months before donation. RESULTS: Recent injection drug use (IDU) was independently associated with HCV infection (29.2% vs. 0% of cases vs. controls, p < 0.001). In addition, likely sources were identified for three other cases (4.6%), including occupational exposure, sexual contact with an HCV-infected partner (who was an IDU), and perinatal exposure, none of which was known to the donors at the time of donation. Incarceration was independently associated with HCV infection among the group not reporting IDU and after removal of the three donors with likely sources of risk (14.6% vs. 1.3% of cases vs. controls, p < 0.001). CONCLUSIONS: A likely risk, primarily IDU, was found for 43 percent of HCV+ donors whose infections were identified solely by NAT. Because the maximum efficiency of the donor history questions may have been reached, NAT will continue to be an important measure to interdict recently infected blood donors.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patients.

The transmission of viral hepatitis from health care workers (HCW) to patients is of worldwide concern. Since the introduction of serologic testing in the 1970s there have been over 45 reports of hepatitis B virus (HBV) transmission from HCW to patients, which have resulted in more than 400 infected patients. In addition there are six published reports of transmissions of hepatitis C virus (HCV) from HCW to patients resulting in the infection of 14 patients. Additional HCV cases are known of in the US and UK, but unpublished. At present the guidelines for preventing HCW to patient transmission of viral hepatitis vary greatly between countries. It was our aim to reach a Europe-wide consensus on this issue. In order to do this, experts in blood-borne infection, from 16 countries, were questioned on their national protocols. The replies given by participating countries formed the basis of a discussion document. This paper was then discussed at a meeting with each of the participating countries in order to reach a Europe-wide consensus on the identification of infected HCWs, protection of susceptible HCWs, management and treatment options for the infected HCW. The results of that process are discussed and recommendations formed. The guidelines produced aim to reduce the risk of transmission from infected HCWs to patients. The document is designed to complement existing guidelines or form the basis for the development of new guidelines. This guidance is applicable to all HCWs who perform EPP, whether newly appointed or already in post.

Schwannoma: challenging diagnosis.

OBJECTIVE: To discuss the presentation of a schwannoma in a 30-year-old man and to discuss the clincial features of this tumor. CLINICAL FEATURES: The patient had lower right back and abdominal pain that was made worse by any jarring motion. Magnetic resonance imaging showed an intradural extramedullary mass of the thoracic spine behind the T10 vertebral body, which was found to be a schwannoma. INTERVENTION AND OUTCOME: A full laminectomy of T10 and partial laminectomies of T9 and T11 allowed removal of the tumor. CONCLUSION: When undiagnosed abdominal pain is present, spinal tumor should be considered one possible diagnosis.

Infection control in hemodialysis units.

Infectious complications of hemodialysis include bacterial infections caused by contaminated water or equipment, other bacterial infections (including vascular access infections), and bloodborne viruses (primarily the hepatitis B and C viruses). Infections caused by contaminated water and equipment can be prevented by a well-designed water-treatment system, routine cleaning and disinfection of system components, and routine bacteriologic monitoring of dialysis water and dialysis fluid. Standard precautions with additional measures recommended specifically for dialysis centers will prevent transmission of bacteria and viruses from patient to patient. These precautions include routine use of gloves, handwashing, and cleaning and disinfection of the external surface of the dialysis machine and other environmental surfaces. In addition, preventing transmission of hepatitis B virus infection requires vaccination of susceptible patients and staff, avoiding dialyzer reuse, and use of a dedicated room, dialysis machine, and staff members when treating patients chronically infected with this virus.

Inhibition of mesothelioma cell growth in vitro by doxycycline.

Malignant mesothelioma causes profound morbidity and nearly universal mortality that is often refractory to conventional treatment modalities of aggressive surgery, radiotherapy, or chemotherapy. Doxycycline, a commonly used antibiotic, has anti-tumor activity against several malignancies, but its anti-tumor effects on malignant mesothelioma have not been evaluated. We report here that concentrations of doxycycline achievable in serum with typical oral doses had cytostatic effects to varying extent on all eight of the mesothelioma cell lines studied but did not affect normal lung fibroblasts. Doxycycline inhibited the production of mitochondrial cytochrome c oxidase, especially in mesothelioma cells more sensitive to its cytostatic effects, and directly inhibited gelatinase A activity; both of these activities are putative mechanisms for the cytostatic activity of doxycycline in other tumor cells. Thus doxycycline may have a role as adjuvant therapy for malignant mesothelioma.