[Atypical keloids with an unusual myofibroblastic differentiation in a patient with acne vulgaris]. / Atypische, Myofibroblasten-reiche Keloide im Rahmen einer Acne vulgaris.

We present the case of a patient with a discreet acne and multiple keloids in the area of the upper trunk, histologically showing an unusual myofibroblastic differentiation. So far, the clinical course shows a poor response to the treatment, including cryotherapy, intralesional corticosteroid injections, occlusive silicone dressings and dye laser.

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia-inducible factor-1α and its central downstream factors.

BACKGROUND: Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. OBJECTIVES: To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. METHODS: The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). RESULTS: HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). CONCLUSIONS: Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

[Extragenital, disseminated infection with human papillomaviruses : Therapeutic response through vaccination with HPV]. / Extragenitale, disseminierte Infektion mit humanen Papillomaviren : Therapeutisches Ansprechen auf HPV-Vakzinierung.

A 50-year-old man with widespread manifestation of warts and distinct pruritus for the last 5 years was diagnosed with a reactivated human papillomavirus (HPV) infection by three, genetically verified types (6, 16, 18), which are included in the vaccine Gardasil®. Conventional treatment was not successful, but a rapid and significant reduction of the skin manifestation was observed after vaccination with Gardasil®. To what extent therapy-resistant infections with HPV can be influenced through an active HPV vaccination should be investigated in future trials.

[Multiple eccrine hidrocystomas on the lower forehead and nose of a 60-year-old man]. / Multiple ekkrine Hidrozystome an Stirn und Nase eines 60-jährigen Mannes.

Multiple eccrine hidrocystomas are benign cystic skin lesions which originate from the sweat gland ducts and typically affect women's midfacial area. Sweating may lead to an increase in size of the translucent papules. In some cases hidrocystomas are associated with other diseases such as Parkinson's disease. Treatment options include laser, topical and systemic anticholinergic drugs (glycopyrrolate, clonidine, atropine, and oxybutynin), whereby therapeutic success is limited in most cases.

Pulmonary, rhino-orbital and cutaneous mucormycosis caused by Rhizomucor pusillus in an immunocompromised patient.

The number of patients with haematopoietic malignancies receiving chemotherapy and stem-cell transplantation has increased the incidence of severe opportunistic infections. Systemic fungal infections are of major concern in immunocompromised patients, as these infections are often fatal. We report a case of a patient with acute myeloid leukaemia who developed multiple cutaneous plaques and necrotizing infiltrates in the lungs during chemotherapy. Using real-time PCR on a wax-embedded tissue sample, Rhizomucor pusillus was identified. We provide an overview of the literature on cutaneous mucormycosis and its diagnosis by PCR.

High-risk human papillomavirus in non-melanoma skin lesions from renal allograft recipients and immunocompetent patients.

BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P<0.001) and basal cell cancers (P=0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P=0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P=0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions.

Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

OBJECTIVE: To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). METHODS: Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. RESULTS: The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. CONCLUSION: These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

[Perianal streptococcal dermatitis caused by ß-hemolytic group G streptococci in two adults]. / Perianale Streptokokkendermatitis durch ß-hämolysierende Streptokokken der Gruppe G bei zwei erwachsenen Patienten.

Perianal streptococcal dermatitis is generally considered a childhood disorder caused by ß-hemolytic group A streptococci. It should also be considered in cases of therapy-refractory gluteal erythema in adults. We report two cases of perianal streptococcal dermatitis in adults. In both, the microbiological examination of the skin swabs showed ß-hemolytic group G streptococci. Therapy of choice is penicillin.

Characterization of regulatory T cells in patients with dermatomyositis.

The purpose of this study was to characterize regulatory T cells (T(reg)) in skin lesions and peripheral blood from patients with dermatomyositis (DM) and to determine the serum levels of regulatory cytokines in the disease. In skin biopsy specimens from patients with DM, immunohistochemistry was performed for CD4(+), CD25(+), forkhead/winged helix transcription factor (FoxP3)(+), transforming growth factor (TGF)-ß(+) and interleukin (IL)-10(+) cells. Additionally, we defined the number of T(reg) subpopulations in peripheral blood by flow cytometry using monoclonal antibodies against CD4, CD25, FoxP3, CD45RO, CD95, CCR4 and CLA. The levels of TGF-ß and IL-10 were also determined in serum samples from patients with DM by enzyme-linked immunosorbent assays. Controls included patients with cutaneous lupus erythematosus, psoriasis and atopic dermatitis (AD) as well as healthy donors. The frequency of FoxP3(+) cells was significantly reduced in skin lesions from patients with DM (p < 0.001) compared to psoriasis and AD. Moreover, the number of cells positive for TGF-ß was lower in DM than in psoriasis and AD, while IL-10(+) cells were significantly reduced only compared to psoriasis. The number of CD4(+)CD25(++)FoxP3(+) T(reg) in the peripheral blood of patients with DM was significantly reduced compared to healthy controls (p < 0.05), whereas other cell populations showed no significant differences. Finally, TGF-ß and IL-10 serum levels were significantly lower in patients with DM compared to healthy controls (p < 0.05). These data suggest that the depletion of T(reg) and their main effector cytokines in the skin and the serum of patients with DM may be an important factor in the pathogenesis of the disease.

[Acne inversa]. / Acne inversa.

Acne inversa is a chronic inflammatory disease of the hair follicles. It can lead to severe functional and psychological impairment. It is characterized by inflamed painful nodules, abscesses, fistulas and scarring in late stages of the disease. The causes of acne inversa are still not fully understood. Conservative treatment options such as antibiotics may lead to clinical improvement; however they do not produce healing. Therapy of choice, especially in severe forms, is radical wide excision of all affected areas. Despite a variety of treatment options, acne inversa is still a therapeutic challenge.

[Verrucous tumor of the amputation stump]. / Verruköser Tumor am Amputationsstumpf.

Epithelioma cuniculatum (EC) belongs to the category of verrucous carcinomas. Invasiveness and rate of metastasis are low, but there is a high risk of local recurrence. In cases of long-standing processes with formation of exophytic, malodorous tumors with jagged edges that do not respond to conventional therapy, consideration should already be given to EC upon visual inspection. The diagnosis is always established by histological examination. The standard treatment of EC is extensive excision of the tumor with micrographic margin control.

[Solid, asymptomatic nodules on several toes in a child]. / Derbe, asymptomatische Knoten an mehreren Zehen bei einem Kind.

The term infantile digital fibromatosis describes a benign tumor of the group of fibromatoses. The prevalence rate is approximately 2.5% of all fibromatoses. The etiopathogenesis of infantile digital fibromatosis is unknown. These tumors can appear already at birth, but usually manifest during the first 3 years of life as solid, pink or skin-colored asymptomatic nodules on one or several fingers or toes. Because of the postoperative recurrence rate of 50-75% and the possibility of spontaneous regression, excision is not recommended according to currently available evidence.

Malignant syphilis with ocular involvement and organism-depleted lesions.

Diagnosis and treatment of syphilis are challenging because of the condition's diverse clinical symptoms, histopathological variance, and the lack of definite tests for treatment follow-up. We report a case of secondary pustular-ulcerative malignant syphilis with ocular involvement in a human immunodeficiency virus-infected patient. It was striking to find that ulcerative lesions can be highly organism depleted.

Fatal varicella in an immunocompromised adult associated with a European genotype E2 variant of varicella zoster virus.

Varicella zoster virus (VZV) seronegative patients under immunosuppressive therapy are at risk for severe life-threatening varicella. A 25-year-old male patient presented with rash and hepatitis. He had been known to suffer from Crohn's disease and received immunosuppressive treatment with azathioprine. The patient showed dyspnoea, and presented with a generalized rash with vesicular lesions typical for herpesvirus infections. He was started immediately on acyclovir therapy. Varicella infection was determined in this VZV seronegative patient in rash vesicles, blood and tracheal secretions and a high VZV viral load was detected in these specimens. The causative agent was genotyped by sequencing of several genes as a variant of the European genotype E2 containing several unique single nucleotide polymorphisms. Despite all measures, there was progressive septic shock, and the patient died due to multi-organ failure. Immunocompromised adults without varicella history are at high risk to develop life-threatening complications of varicella. Antiviral therapy with acyclovir can only be successful when administered as early as possible on suspicion of varicella infection in this group of patients. The most effective method to prevent severe varicella in immunocompromised patients is active immunization prior to immunosuppressive therapy.

Successful surgical management of giant condyloma acuminatum (Buschke-Löwenstein tumor) in the genitoanal region: a case report and evaluation of current therapies.

Giant condyloma acuminatum (GCA; Buschke-Lowenstein tumor) is a human-papillomavirus-induced cauliflower-like tumor of the genitoanal region. It is characterized by its size, capability of local infiltration and high recurrence rate. We report on a 50-year-old patient presenting with a maximum finding of GCA with deep infiltration into the adductor and perineal musculature, the scrotum, the penis and the para-rectum. After performing a temporary loop colostomy, the tumor was removed by wide radical excision following plastic reconstruction with a myocutaneous gracilis flap. During a follow-up period of more than 5 years, no recurrence developed. Many treatment strategies (e.g. chemotherapy, radiation) have been published in the literature. Most authors recommend the radical surgical excision, allowing a complete histological examination and assessment of tumor-free resection margins. Despite the benign histological pattern of GCA in most cases, transformations into verrucous carcinoma and squamous-cell carcinoma have been described. In our case, the GCA seems to represent a continuum between normal condyloma acuminatum and an initial verrucous carcinoma.

[Inflammatory stage of disseminated superficial porokeratosis in a 71-year old patient]. / Eruptive inflammatorische disseminierte Porokeratose bei einer 71-jährigen Patientin.

The inflammatory stage of disseminated superficial porokeratosis is a rare disease, which has only been described in case reports, primarily affecting Japanese patients. After having asymptomatic disseminated superficial porokeratosis for years, a typical patient then experiences a sudden exacerbation with distinct pruritus. Histologically, the lesions may show eosinophilic spongiosis in addition to the characteristic cornoid lamella. We describe a 71-year old patient with clinically and histologically diagnosed inflammatory stage of disseminated superficial porokeratosis.