Segmental Erythema Multiforme: An Unusual Drug Reaction to Anastrozole.

Erythema multiforme (EM) is an immune-mediated, mucocutaneous hypersensitivity syndrome that can occur as a result of various medications, including a wide range of antineoplastic and hormonal drugs. Anastrozole, a nonselective aromatase inhibitor used in breast cancer management has been associated with different cutaneous side effects, of which EM is rarely seen and usually in a minor or major form with typical target lesions. This is a short report of a patient who developed a rare cutaneous side effect after the use of aromatase inhibitor anastrozole - segmental erythema multiforme in cancer-affected area. Cutaneous adverse effects limited to cancer-affected breast are extremely rare but should be considered in everyday dermatological practice. We find this case instructive not only because of the rarity of the segmental EM, but also because, contrary to classical teaching, drug eruption due to anastrozole occurred months, not days after the initiation of therapy.

Vemurafenib and cobimetinib-induced toxic epidermal necrolysis in a patient with metastatic melanoma.

Combination therapy in the treatment of metastatic melanoma has been associated with more durable response rate compared to monotherapy. However, previous studies have shown that combined target therapy commonly causes a wide spectrum of adverse events. These adverse reactions are usually manageable, however, it is always necessary to compare drug efficacy with its potential adverse effects. Toxic epidermal necrolysis represents severe mucocutaneous reaction, usually triggered by medications and characterized by extensive necrosis and detachment of the epidermis. Here we present a first case of toxic epidermal necrolysis induced by combined target therapy (vemurafenib plus cobimetinib). The case was observed in a young patient with BRAF mutant melanoma who was started on first-line metastatic immunotherapy with pembrolisumab.

Potential hot spot for de novo mutations in PTCH1 gene in Gorlin syndrome patients: a case report of twins from Croatia.

We describe a case of twins with sporadic Gorlin syndrome. Both twins had common Gorlin syndrome features including calcification of the falx cerebri, multiple jaw keratocysts, and multiple basal cell carcinomas, but with different expressivity. One brother also had benign testicular mesothelioma. We propose this tumor type as a possible new feature of Gorlin syndrome. Gorlin syndrome is a rare autosomal dominant disorder characterized by both developmental abnormalities and cancer predisposition, with variable expression of various developmental abnormalities and different types of tumors. The syndrome is primarily caused by mutations in the Patched 1 (PTCH1) gene, although rare mutations of Patched 2 (PTCH2) or Suppressor of Fused (SUFU) genes have also been found. Neither founder mutations nor hot spot locations have been described for PTCH1 in Gorlin syndrome patients. Although de novo mutations of the PTCH1 gene occur in almost 50% of Gorlin syndrome cases, there are a few recurrent mutations. Our twin patients were carriers of a de novo mutation in the PTCH1 gene, c.3364_3365delAT (p.Met1122ValfsX22). This is, to our knowledge, the first Gorlin syndrome-causing mutation that has been reported four independent times in distant geographical locations. Therefore, we propose the location of the described mutation as a potential hot spot for mutations in PTCH1.

[Pyoderma gangrenosum: case report]. / Pyoderma gangrenosum--prikaz bolesnika.

A 56-year-old patient presenting necrotic ulcerations on the right leg was admitted to our Department for physical status deterioration. Clinically suspected diagnosis of pyoderma gangrenosum was confirmed histologically. Considering the association of pyoderma gangrenosum with several systemic diseases, extensive diagnostic evaluation was performed. Colonoscopy showed multiple ulcerations on descendent colon with stenosis of the shorter segment. Histologic examination confirmed the diagnosis of Crohn's disease. After systemic treatment with corticosteroids and wound management with proper wound dressings, complete epithelialization of ulcerations was accomplished.

[Squamous cell carcinoma--case report]. / Planocelularni karcinom--prikaz bolesnika.

Carcinoma that develops in chronic ulcers, wounds, burn scars and fistulas is known as Marjolin's ulcer. It occurs primarily as a squamous cell carcinoma and rarely as basal cell carcinoma. Marjolin's ulcer represents 2% to 5% of all squamous cell carcinomas of the skin. We present a 60-year-old male patient with chronic ulceration on the right leg. The ulceration appeared 15 years before at the localization of the burn scar following an injury and was treated for years as a chronic venous ulcer. After sudden enlargement of the ulcer, biopsy confirmed it to be invasive squamous cell carcinoma. Ultrasound and computed tomography revealed a metastatic squamous cell carcinoma in the inguinal lymph node. After complete excision of the tumor and inguinal lymph node dissection, the patient was under supervision of the surgeon and oncologist because of tumor relapse on the skin and lymph node. This case should serve as a reminder to practitioners to perform biopsy of every ulcer that fails to heal or when other risk factors for venous ulcers are missing, in order to avoid delay in diagnosis and complications.

A case report of an unrecognized nevoid melanoma in a young woman--clinicopathological diagnostic challenge.

Nevoid melanoma is a rare form of melanoma histologically resembling benign melanocytic nevi and may be overlooked in routine histological sections. Authors are presenting a case of a 31-year-old woman who presented with bizarre pigmented skin lesions in the area of the postoperative scar on the back where, 6 years earlier, a "nevus pigmentosus epidermo-dermalis" was excised and hystologically confirmed in outer institution. The lesions were surgically removed and histopathological findings were characteristic for nevoid melanoma. Additionally, specimen of primary removed lesion was reexamined and primary nevoid melanoma was then recognized, therefore indicating that the lesions our patient presented with are nevoid melanoma recidivisms. Extensive diagnostic procedures showed no signs of melanoma dissemination. Three months later, the patient returned for consultation and presented with two new brownish-pigmented papules in the area of the new postoperative scar. The lesions were excised and new nevoid melanoma recidivism was confirmed. The patient remained under the regular follow up and, almost 9 years after the removal of primary nevoid melanoma, followed by two cutaneous recidivisms, remains disease-free. This case aims to highlight the problematic area in the analysis of pigmented skin lesions where nevoid melanoma represents one of the clinical and pathological diagnostic challenges.

Multiple angiokeratomas of the vulva: case report and literature review.

Angiokeratomas of the vulva are relatively rare finding and a limited number of cases have been reported in the literature. Clinically, angiokeratomas of the vulva are benign vascular lesions usually occurring in middle-aged or older women. Microscopically these lesions are characterized by epidermal hyperkeratosis, papillomatosis, acanthosis, and marked dilatation of the papillary dermal vessels. In most patients, genital lesions are asymptomatic; however, bleeding, dyspareunia and other symptoms have been described. We report a case of a 45-year-old woman with numerous blue-to-red, scaly papules that spread over the entire area of both labia majora. The patient reported occasional pruritus and burning sensations, discomfort during the intercourse, and significant psychological burden. Histopathologic analysis of the lesion confirmed the diagnosis of angiokeratoma, and all lesions were electrocauterized under local anesthesia. The results of the treatment were very satisfactory, with no side effects or complications. During one-year follow-up, no relapses were noted and the patient remained asymptomatic. Therefore, dermatovenereologists should be aware of angiokeratomas and respective therapeutic options when examining a patient with pruritic, painful, or bleeding lesions in the genital region.

New option in photoprotection.

All the people are exposed to solar ultraviolet radiation. Exposure to sun with living in an oxygen-rich atmosphere causes unwanted photodemage. Sunburned skin is a leading risk factor for melanoma and non-melanoma cancers. UV exposure causes immunosuppression via multiple mechanisms in the skin. In this review the main topic is to mention new or alternative ways of photoprotection. Sunscreens are commonly used as protection against sun damage. They reduce the penetration of damaging solar UV wavelengths in skin by reflecting or absorbing them. Sunscreens are very valuable, but they have limitations. They have to be used properly to gain the full effect (application a little while before UV exposure, at frequent time points and in adequate amounts). Also, they have the problem of photoinactivation, which is the degeneration of the UV-filter due to exposure to UV rays resulting in the loss of absorbing capacity. Products with immune protection factor contain DNA-repair enzymes and antioxidants that may reduce mutations and enable the immune system to combat photodamage. The use of antioxidants and polyphenols may exert an anti-aging effect by preventing and even reversing sun damage. Adequate photoprotection is essential to control photocarcinogenesis and photoaging.

Photosensitivity skin disorders in childhood.

Photosensitivity in childhood is caused by a diverse group of diseases. A specific sensitivity of a child's skin to ultraviolet light is often the first manifestation or a clinical symptom of photodermatosis. It might indicate a serious underlying systemic disease such as lupus erythematosus or dermatomyositis, or a rare group of genetic skin disorders like Xeroderma pigmentosum, Cockayne syndrome, Trichothyodystrophy, Bloom syndrome, Rothmund-Thomson and Kindler syndrome as well as metabolic disorders and cutaneous porphyria. Photosensitivity secondary to topical or systemic agents may also cause photosensitivity in children. Early recognition and prompt diagnosis may prevent complications associated with unprotected exposure to sunlight and avoid actinic injuries that can lead to malignant skin changes.

Prevention of complications in dermatosurgery.

Dermatosurgery has become ever more popular and important in recent years, mostly due to the increasing prevalence of skin malignancies. It also encompasses a wide variety of methods to remove or modify skin tissue for numerous cosmetic reasons. Nowadays, many dermatologists provide complete dermatologic care for their patients, including surgery. Therefore, it is important to be aware of the possible complications and to be able to manage them properly. Complications in cutaneous surgery are not very often, but they can be serious and worrisome including bleeding, infections, allergic reactions, syncope, wound dehiscence, necrosis, and others. In this article special attention is given to bleeding, which is the most common complication in this field. The best way to reduce the number of possible complications is to recognize patients at risk. Thus, complete history and physical examination are required before performing any dermatosurgical operation.

Vitamin D--the true and the false about vitamin D.

Vitamin D has a positive impact on our overall health. Also there are a few conditions with strong evidence for a protective effect of vitamin D, such as bone diseases, internal cancers, multiple sclerosis, hypertension and DM type 1. Skin is the major source of vitamin D through the action of UVB light on keratinocytes, although the biologically active form of vitamin D is not exclusively produced in the kidney but also in prostate, colon, skin and osteoblast where it acts as an autocrine or paracrine hormone. In the past decade raising incidence of skin cancers, especially melanoma and its connection with sun exposure lead to a sun protection policies and practices as part of the public health campaigns. The question is how much solar UV exposure is adequate to maintain the balance between the risk and the benefit. We as dermatologists have to raise public awareness of the potential health effects from excessive exposure to UV radiation but also we have to be aware that adequate blood level of vitamin D is necessary for optimal health. So future recommendation on sun protection have to balance between the risk and benefits of sun exposure, as well as to promote vitamin D supplementation as a safe alternatives in high risk population.

Photoaging.

Among harmful environmental factors that contribute to extrinsic aging, long-term effects of repeated exposure to ultraviolet light are the most significant and are referred to as photoaging. Photoaging is a multisystem degenerative process that involves the skin and skin support system. It is a cumulative process and depends primarily on the degree of sun exposure and skin pigment. The epidermis and dermis are both affected by UVB, but the dermis is also affected to a significant extent by UVA. It has long been thought that the majority of human photo-lesions due to UVB rays, now it is believed that UVA play a substantial role in photoaging. Photoaging affects the sun-exposed areas and is characterized clinically by fine and coarse wrinkling, roughness, dryness, laxity, teleangiectasia, loss of tensile strength and pigmentary changes. There is also an increase in development of benign and malignant neoplasms on photoaged skin. During the years the progress has been made in understanding the photoaging in human skin. UV irradiation invokes a complex sequence of specific molecular responses that damage skin connective tissue. Restriction of UV irradiation and the use of high-protection, broad-spectrum sunscreens may slow progression of photoaging.

Unrecognized cicatricial pemphigoid with oral manifestations and ocular complications. A case report.

Cicatricial pemphigoid is an autoimmune bullous disease characterized by mucous membrane fibrosis with resulting scarring, predominantly in the conjunctival and oral mucosa, which rarely involves skin changes. The majority of patients present with painful erosions or desquamative scarring gingivitis, resulting in eating and drinking disorders. Typical ocular lesions include chronic scarring conjunctivitis with progressive subconjunctival fibrosis, fornix foreshortening and synechia formation between the bulbar and palpebral conjunctiva, occasionally resulting in blindness. A 69-year-old woman was admitted to our Department for intense pain and severe burning sensation in the oral cavity, induced by several erosions and solitary blisters, lasting for 3 years. She was also diagnosed with the right eye symblepharon, lid entropion, trichiasis, leukoma and blindness of the right eye. The diagnosis of cicatricial pemphigoid was based on clinical picture and histopathology combined with immunofluorescence methods, with therapy initiated thereupon. Systemic corticosteroid (methylprednisolone) therapy in combination with azathioprine proved successful in the treatment of oral lesions as well as for stabilization of ocular lesions. Unfortunately, the patient was diagnosed in the advanced stage when scarring had already occurred. Prompt recognition of cicatricial pemphigoid and close patient monitoring are an imperative for the future prognosis of the disease.

Results of the determination of serum markers in patients with malignant melanoma.

Although there is no routine procedure for determination of serum markers in patients with malignant melanoma (MM), some markers are being studied as potentially useful prognostic tools. Serum lactate dehydrogenase (LDH), protein S-100B, melanoma-inhibiting activity (MIA) and tyrosinase may correlate with melanoma progression. In this study, the results of determination of S100 protein, LDH, MIA and tyrosinase in the serum of 50 patients with MM (stages I-IV) were determined. The increased values of MIA were found in 26% patients in stage I, while in 50% patients in stage IV Increased S-100 protein was found in 13% patients in stage I while in 50% patients in stage IV. The increased values of LDH were found in 26% patients in stage I, while in 25% patients in stage IV. The positive serum tyrosinase was noticed in 17.3% patients in stage II, while in 25% patients in stage IV. The obtained results have revealed no significant differences between the groups in higher and lower stages of the disease, indicating that blood markers are not reliable prognostic factors for MM progression.