[Alopecia due to chemotherapeutics, hedgehog inhibitors, targeted antibody therapies and immune checkpoint inhibitors : Pathogenesis, clinical picture, diagnostics and prophylaxis]. / Alopezie durch Chemotherapeutika, Hedgehog-Inhibitoren, zielgerichtete Antikörpertherapien und Immuncheckpointinhibitoren : Pathogenese, Klinik, Diagnostik und Prophylaxe.

BACKGROUND: The incidence and severity of alopecia vary mainly depending on the chemotherapeutic agent used or other drug groups. The pathogenetic characteristics of the different forms of alopecia are reflected in the clinical presentation and, in some cases, in the resulting recommendations for prophylaxis. OBJECTIVES: To provide an overview of the pathogenesis, clinical presentation, diagnosis and prophylaxis of alopecia with chemotherapeutic agents, hedgehog inhibitors, targeted therapies and immune checkpoint inhibitors. MATERIALS AND METHODS: Based on the current S3 guideline "Supportive therapy", an extensive literature search was carried out. RESULTS AND CONCLUSION: Chemotherapy-induced hair loss (CIA) occurs in up to 65% of cases. Anagen effluvium is observed as early as 1-3 weeks after the start of treatment and is reversible in most cases. Alopecia associated with inhibitors of the Sonic Hedgehog signaling pathway (HHIA) such as vismodegib or sonidegib are observed in up to 60% of cases. They are characterized by telogen effluvium. BRAF or immune checkpoint inhibitors lead significantly less frequently to alopecia (BRAFA, CPIA). According to taxane-based chemotherapy protocols, scalp cooling can help to prevent higher-grade CIA. If CIA or other forms of alopecia are expected, early contact with self-help organizations and early prescriptions for wigs should be offered.

Preferences of German and Swiss melanoma patients for toxicities versus melanoma recurrence during adjuvant treatment (GERMELATOX-A-trial).

PURPOSE: Adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) ± CTLA4-antibodies (cICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in disease-free survival (DFS). Due to specific side effects, the choice of treatment is very often driven by the risk for toxicity. This study addressed for the first time in a multicenter setting the attitudes and preferences of melanoma patients for adjuvant treatment with (c)ICI and TT. METHODS: In this study ("GERMELATOX-A"), 136 low-risk melanoma patients from 11 skin cancer centers were asked to rate side effect scenarios typical for each (c)ICI and TT with mild-to-moderate or severe toxicity and melanoma recurrence leading to cancer death. We asked patients about the reduction in melanoma relapse and the survival increase at 5 years they would require to tolerate defined side-effects. RESULTS: By VAS, patients on average valued melanoma relapse worse than all scenarios of side-effects during treatment with (c)ICI or TT. In case of severe side effects, patients required a 15% higher rate of DFS at 5 years for (c)ICI (80%) compared to TT (65%). For survival, patients required an increase of 5-10% for melanoma survival during (c)ICI (85%/80%) compared to TT (75%). CONCLUSION: Our study demonstrated a pronounced variation of patient preferences for toxicity and outcomes and a clear preference for TT. As adjuvant melanoma treatment with (c)ICI and TT will be increasingly implemented in earlier stages, precise knowledge of the patient perspective can be helpful for decision making.

[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.

[Pyogenic granuloma with satellitosis]. / Satellitenrezidiv bei Granuloma pyogenicum.

A 16-year-old female developed a satellite-like recurrence of a pyogenic granuloma on her thorax 2 weeks after complete excision. Treatment with a pulsed dye laser led to a complete resolution. BRAF and RAS mutations detected in the pyogenic granuloma are considered major driver mutations. Whether these findings are also of importance for the etiopathogenesis of satellitosis is unknown. In our patient, no BRAF or NRAS mutation could be detected.

Cutaneous squamous cell carcinoma (cSCC) and immunosurveillance - the impact of immunosuppression on frequency of cSCC.

Solid organ transplant recipients (OTR) are at extreme risk of developing cutaneous squamous cell carcinomas (cSCC) post-transplantation due to the immunosuppressive medication needed to retain the transplanted organ. The early classical immunosuppressive drugs, azathioprine and cyclosporine, have largely been replaced by modern immunosuppressants, namely mycophenolate mofetil and tacrolimus, as well as sirolimus and everolimus. Although still very high, the risk of cSCC in OTR seems to be decreasing which suggests that cSCC risk may be lower in OTR treated with these modern immunosuppressive drugs and that cSCC preventive measures may be effective. OTR should be closely monitored so that cSCC can be treated at an early stage. (Chemo)prevention of cSCC as well as changing immunosuppression to more favourable regimens will be important in future to reduce skin cancer incidence.

[Skin cancer screening and treatment costs : Utilisation of the skin cancer screening and skin cancer treatment costs in organ transplant recipients]. / Hautkrebsscreening und Behandlungskosten : Inanspruchnahme des Hautkrebsscreenings und Kosten der Hautkrebsbehandlung bei organtransplantierten Patienten.

BACKGROUND: Organ transplant recipients have an up to 250-times higher risk to develop skin cancer. This article evaluated the utilisation of skin cancer screening and the treatment costs for skin cancer in organ transplant recipients. Patients of the health insurance AOK Bremen/Bremerhaven had been identified and the need for skin cancer prevention trainings was derived. METHODS: The number of organ transplant recipients (ICD code Z94.0-4) with and without any history of skin cancer (ICD code C43/C44), the utilisation of dermatologic health care services, and the costs for treatments with the diagnosis Z94.0-4 with and without C43/C44 were evaluated. The analyses were carried out for the period from 2009-2014 by using the accounting systems of the AOK. RESULTS: Between 2009 and 2014, 231 organ transplant recipients had been recorded. By mid-2014, 20% of these insured persons developed skin cancer and the mean incidence was 2.76% per year. On average, 43% of these patients were seen by a dermatologist at least once a year, whereby only 15% of the organ transplant recipients participated in the annual skin cancer screening. In 29% of the patients without any history of skin cancer, a skin examination was never performed by a dermatologist or a general practitioner. In all, 17 inpatient cases of organ transplant recipients with the primary diagnosis C43/C44 were analyzed. This resulted in total costs of 54,707 € (on average about 3200 € per case). CONCLUSIONS: The increased incidence of skin cancer and the associated treatment costs indicate the need for skin cancer prevention training.

[Bullosis diabeticorum : Two case studies]. / Bullosis diabeticorum : Zwei Kasuistiken.

We report two cases of patients with diabetes mellitus who developed bullae measuring 2 cm in diameter on the fingers or toes, which could be classified as bullosis diabeticorum after excluding several differential diagnoses that are discussed. Bullosis diabeticorum is a rare blister formation located on the palmoplantar region, which is mainly observed in the case of diabetic patients. The clinical picture is characterized by tense bullae measuring up to 10 cm in diameter, containing clear to hemorrhagic fluid. Generally, lesions heal without residual scarring, less frequently with residual postinflammatory pigmentation or tender scars. On histopathological examination, both intraepidermal and subepidermal bullae are found without any significant inflammatory infiltrate. The etiopathogenesis of bullosis diabeticorum has not yet been clarified.

[Segmental neurofibromatosis]. / Segmentale Neurofibromatose.

Thirteen years ago, a 48-year-old man developed numerous neurofibromas in a circumscribed area on the right chest. At the same time, a bilateral seminoma was diagnosed and treated curatively. There was no evidence for other complications of neurofibromatosis. The family history was inconspicuous. The segmental neurofibromatosis (SN) presented in this patient is the result of a mosaic formation resulting from a mutation of the NF1 gene, a tumor suppressor gene. Concomitant, typical diseases of neurofibromatosis generalisata (NFG), including malignant neoplasms, are the exception to SN.

[Pilomatrixoma in a tattoo]. / Pilomatrixom in einem Tattoo.

A 31-year-old man developed a fast-growing tumor on the right upper arm within a black tattoo, which could be classified histologically as pilomatrixoma. While the age of the patient and the rapid growth of the tumor cannot be regarded as typical findings of pilomatrixomas, the localization on the upper arm is one of their predilection points. Despite the wide spread use of tattoos in the last few decades, tumor development in tattooed skin is rarely reported. It is still controversial whether the ingredients of the tattoo agents can be responsible for tumor induction.

[Generalized circumscribed scleroderma with blisters]. / Generalisierte zirkumskripte Sklerodermie mit Blasenbildung.

The patient suffered from a 20-year course of generalized circumscribed scleroderma and presented with blisters in circumscribed areas of the affected skin. The development of subepidermal blisters has been described in all clinical forms of circumscribed scleroderma. Aetiology and pathogenesis of blister formation have not yet been clarified. An obstruction of the lymphatic vessels due to the present sclerosis is favoured. Treatment of bullous circumscribed scleroderma is considered to be difficult. Oral steroids, methotrexate, hydroxychloroquine and PUVA methods have been used with varying success.

[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.

[Frontal fibrosing alopecia]. / Frontal fibrosierende Alopezie Kossard.

Within the group of cicatricial alopecias, Kossard first described frontal fibrosing alopecia (FFA) in 1994 as a variant of lichen planopilaris (LPP). This classification is based on the histopathological findings of FFA and LPP, which are identical and therefore not separable. The clinical picture of FFA, however, is very characteristic and marked by regionally distinct structures of the skin. Typically, postmenopausal women present with a band-shaped atrophy that is several centimeters wide located in the frontotemporal area. Adjacent to the hairline, perifollicular erythema and papules can be found. In the majority of patients there is a loss of the eyebrows. Circumscribed alopecia and perifollicular papules occur only rarely on the extremities or the trunk. Etiology and pathogenesis of FFA are unclear. Hormone-related involutionary phenomena of the follicle, genetic factors, disruption of lipid homeostasis, and in accordance with the lichen planus associated T­cell cytotoxic autoimmune response are discussed. Treatment of FFA is difficult. Atrophy cannot be influenced by the currently available treatment options. With regard to the follicular inflammation, topical steroids and systemic hydroxychloroquine, antiandrogens, and tetracyclines are mainly used on a topical basis.

[Tattooing agents and adverse reactions]. / Tätowiermittel und ihre Unverträglichkeitsreaktionen.

BACKGROUND: Tattoos are regarded as body jewelry and have become widespread in all parts of society. Despite introduction of the tattooing agents' regulation (Tätowiermittelverordnung) in Germany in 2009, consumer protection is incomplete. OBJECTIVES: Prevalence of tattoos and their legal basis, ingredients of tattooing agents, clinical findings of adverse reactions, pathogenesis and therapy. METHODS: The work is based on a selective literature search in PubMed and on the clinical experience of the authors. RESULTS: Adverse reactions by tattooing are a particular problem, because the causing substances are not biodegradable within the tissue. In addition to an agonizing pruritus, the clinical picture is characterized by erythematous plaques. Histopathology reveals different patterns of inflammation, including pseudolymphomatous reactions. Treatment is problematic. In many cases, extensive surgical excision is necessary, which is associated with cosmetic consequences. CONCLUSION: A regulation to assess the safety of tattooing does not exist.

[Verrucous variant of porokeratosis of Mibelli as a differential diagnosis of psoriasis vulgaris]. / Verruköse Variante der Porokeratosis Mibelli als Differenzialdiagnose der Psoriasis vulgaris.

In a 37-year-old man, diagnosis of verrucous porokeratosis could only be made by histological examination. Previously, the skin lesions on the right buttock had been treated by several dermatologists as psoriasis vulgaris. The clinical picture of both dermatoses was characterized by sharply defined, erythematous papules and plaques. Precise evaluation of the clinical morphology was key for diagnosis. Moreover, in contrast to psoriasis, verrucous porokeratosis is characterized by a high degree of treatment resistance.

[Leukonychia totalis]. / Leukonychia totalis.

Our patient presented with leukonychia totalis at the age of 15 years. Other malformations such as syndromes or underlying internal diseases did not exist. The patient's family history was unremarkable. In the classification of leukonychias, the real, usually hereditary leukonychia can be distinguished from the acquired form. The white color of the nails can be isolated, depending on its present form, appear as part of a syndrome, or as a result of internal disease. An effective treatment of hereditary leukonychia is not known.

[Subcutaneous panniculitis-like T-cell lymphoma : Two case reports]. / Subkutanes pannikulitisartiges T-Zell-Lymphom : Zwei Kasuistiken.

Histopathology, immunohistochemical, and molecular genetic findings revealed the diagnosis of subcutaneous panniculitis-like T-cell-lymphoma in two patients, aged 44 and 70 years. The clinical morphology of the lymphoma manifestations showed varied significantly. One patient presented with a singular erythematous nodule in the chin region. The other patient suffered from extended plate-like resistances and atrophy of the face, upper arms and left breast. Hemophagocytic syndrome was not present in either patient. Prognosis of subcutaneous panniculitis-like T-cell lymphoma without associated hemophagocytic syndrome is reported to be favorable. Radiotherapy of the singular lesion on the chin and systemic corticosteroids of the extended plaques induced complete remission in both patients.

[Perianal and rectal ulcers due to abuse of paracetamol-codeine suppositories]. / Perianale und rektale Ulzera nach Abusus von Paracetamol-Codein-Suppositorien.

A 61-year-old woman presented with a progressive perianal ulcer which had developed 4 months ago. Upon further examination, another ulcer of the rectum was detected. Anorectal malignancies, viral infections or primary inflammatory bowel disease were not found. It could be demonstrated that the ulcers were induced by paracetamol and codeine suppositories. After discontinuation of these suppositories, the perianal ulcers healed almost completely within 3 weeks. The pathogenesis of paracetamol-induced ulcers is unknown. However, dose-dependent vasoconstriction is a possible explanation.

[Childhood granulomatous periorificial dermatitis]. / Granulomatöse periorifizielle Dermatitis der Kindheit.

CASE REPORT: A 14-year-old patient of African ancestry presented with multiple papules in the perioral, perinasal and periocular areas. Histopathology showed sarcoidal granulomas. DIAGNOSIS: After exclusion of systemic sarcoidosis, the diagnosis of childhood granulomatous periorificial dermatitis was made. THERAPY: Topical treatment with erythromycin resulted in complete regression. CONCLUSION: Childhood granulomatous periorificial dermatitis is mainly observed in dark-skinned children of African, Caribbean, or Asian origin. The nosological position of the dermatosis is controversial. Originally classified as sarcoidosis, childhood granulomatous periorificial dermatitis is now generally regarded as a special form of perioral dermatitis.

[Drug-induced subacute cutaneous lupus erythematosus: repeated occurrence following treatment with terbinafine]. / Arzneimittelinduzierter subakuter kutaner Lupus erythematodes : Wiederholtes Auftreten nach Einnahme von Terbinafin.

A woman developed subacute cutaneous lupus erythematosus (SCLE) in 1995 and 2013, each time 6 weeks after initiation of terbinafine therapy. Within the heterogeneous group of drug-induced SCLE terbinafine is considered the most common cause. The clinical, histopathological and laboratory findings of idiopathic and drug-induced SCLE are largely identical. The pathogenesis of drug-induced SCLE is not known. Cytotoxic and immunological mechanisms are considered likely. The treatment of drug-induced SCLE is discontinuation of the suspected drug. In addition, corticosteroids are recommended alone or in combination with chloroquine or hydroxychloroquine.