Huriez syndrome: Additional pathogenic variants supporting allelism to SMARCAD syndrome.

Huriez syndrome (HRZ, OMIM181600) is a rare genodermatosis characterized by scleroatrophic hands and feet, hypoplastic nails, palmoplantar keratoderma, and predisposition to cutaneous squamous cell carcinoma (cSCC). We report herein three HRZ families from Croatia, the Netherlands, and Germany. Deep sequencing followed by Sanger validation, confirmed the presence of germline causative SMARCAD1 heterozygous pathogenic variants. All seven HRZ patients displayed hypohidrosis, adermatoglyphia, and one patient developed cSCC at 32 years of age. Two novel monoallelic germline mutations were identified which are predicted to disrupt the first exon-intron boundary of the skin-specific SMARCAD1 isoform. On the basis of phenotypic and genotypic convergence with Adermatoglyphia (OMIM136000) and Basan syndrome (OMIM129200), our results lend credence to the notion that these three Mendelian disorders are allelic. We propose adding Huriez syndrome to the previously suggested SMARCAD syndrome designation, which was originally invoked to describe the spectrum of monogenic disorders between Adermatoglyphia and Basan syndrome.

CAN SKIN BE A MARKER FOR INTERNAL MALIGNANCY? EVIDENCE FROM CLINICAL CASES.

Although there are many single case reports on paraneoplastic dermatoses in the literature, there are very rare articles containing multiple cases. A retrospective study was performed to examine paraneoplastic dermatoses and accompanying malignancies based on skin manifestations and appropriate diagnostic evaluations. We recorded outcomes, current conditions, and surgical/oncologic treatments. Analysis revealed paraneoplastic dermatoses in 17 patients with various skin lesions, i.e. eczematous dermatitis, vasculitis, subacute cutaneous lupus erythematosus, pruritus, chronic urticaria/angioedema, alopecia areata, flushing, bullous pemphigoid, dermatomyositis, and localized scleroderma (morphea). They were associated with different solid and hematologic malignancies (3 gastric, 2 prostate, 2 bladder, 2 thyroid, and 2 lymphoma), along with 1 case each of the following: lung, hepatocellular, esophageal, endometrial, kidney, and multiple myeloma. The majority of skin lesions gradually regressed after malignancy treatment. To our knowledge, our three cases of paraneoplastic eczematous dermatitis are the first to be associated with gastric, prostate and endometrial cancer. Additionally, we report a case of a patient with alopecia areata of the beard associated with thyroid cancer. Early malignancy detection based on skin markers makes early introduction of surgical/oncologic therapy possible and usually leads to skin lesion regression while reducing revolving door visits to specialists and the (financial) burden on the healthcare system.

[QUALITY OF LIFE AND PSYCHOLOGICAL ASPECTS IN PATIENTS WITH CHRONIC LEG ULCER]. / KVALITETA ZIVOTA I PSIHOLOSKI ASPEKTI U BOLESNIKA S KOZNIM VRIJEDOM.

Wound represents a disruption of anathomic and physiologic continuity of the skin. Regarding to the healing process, wounds can be classified as acute or chronic wounds. Quality of life is primarily concerned with the impact of chronic wounds. A wound is considered chronic if healing does not occur within expected period of time regarding to its etiology and localization. Chronic wounds can be classified as typical and atypical. The majority of wounds (95 percent) are typical ones which include ischaemic, neurotrophic and hypostatic ulcer and two separate entities: diabetic foot and decubital ulcers. An 80 percent of chronic wounds localized on lower leg are result of chronic venous insufficiency, in 5-10 percent cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Chronic wounds represent a significant burden to patients, health care professionals and the entire health care system. Chronic wounds affect the elderly population and it is estimated that 1-2 percent of western population suffer from it. This estimate is expected to rise due to an increasing population of the elderly and the diabetic and obesity epidemic. The WHO definition of health is "A state of complite physical, mental and social well-being and not merely the absence of disease or infirmity". Based on this definition, quality of life in relation to health may be defined as "the functional effect of an illness and it's consequent therapy upon a patient, as perceived by the patient". The domains that contribute to this effect are physical, psychological and social functioning. The patient's own perceptions of an illness were found to play an important role in explainig quality of life. Chronic wounds significantly decrease the quality of life in a number of ways such as reduced mobility, pain, unpleasant odor, sleep disturbances, social isolation and frustration, and inability to perform everyday duties. Among the most common psychological reactions to chronic diseases, including chronic wounds, are depression, anxiety, aggression and frustration. Psychological factors may not only be a consequence of delayed healing, but may also impact on wound healing. Anxiety and depression have direct influences on endocrine and immune function. About the impact of disease on quality of life and individuals' perceptions of illness, there are questionnaires and methods to analyze this, but the challenge is to move from a focus on wound management to understanding the specific needs of each individual within the context of their life.

[Differential diagnosis and work up of chronic leg ulcers]. / Diferencijalna dijagnoza i dijagnosticki postupci kod kronicnih rana na potkoljenici.

Many factors contribute to the pathogenesis of leg ulcers. The main causes are chronic venous insufficiency, peripheral arterial occlusive disease (PAOD) and diabetes. Some leg ulcers are caused by combinations of these well-known etiologic factors. The most common cause of PAOD is arteriosclerosis. In diabetic patients, distal symmetric neuropathy and peripheral vascular disease are probably the most important etiologic factors in the development of leg ulcers. Less frequent causes of chronic leg ulcers are hematologic diseases, autoimmune diseases, genetic defects, infections, primary skin disease, cutaneous malignant diseases, use of some medications and therapeutic procedures, and numerous exogenous factors. Diagnosis of leg ulcer is made upon medical history, clinical picture, palpation of arteries, functional testing and serologic testing. Device-based diagnostic testing should be performed for additional clarification. Also, lesion biopsy should be taken for histopathology, direct immunofluorescence, bacteriology and mycology. The knowledge of differential diagnosis is essential for ensuring treatment success in a patient with leg ulcer.

Cutaneous Hyalohyphomycosis and Its Atypical Clinical Presentations in Immunosuppressed Patients.

There has been a substantial increase in the number of cases of invasive fungal infections worldwide, which is associated with a growing number of immunosuppressed patients and a rise in antifungal resistance. Some fungi that were previously considered harmless to humans have become emerging pathogens. One of them is Purpureocillium lilacinum, a ubiquitous filamentous fungus commonly found in the environment, especially in the air and soil. P. lilacinum belongs to a bigger group of hyaline fungi that cause hyalohyphomycosis, a fungal infection caused by fungi with colorless hyphae. Although this is a heterogeneous group of fungi, there are similarities regarding their ubiquity, ways of transmission, affected patients, and difficulties in diagnostics and treatment. In hyalohyphomycosis, the skin is one of the most affected organs, which is why the involvement of dermatologists is crucial for the initial assessment, since the timely recognition and early diagnosis of this condition can prevent life-threatening infections and death. In this review, we covered cutaneous hyalohyphomycosis caused by P. lilacinum and other fungi in the same group, including Fusarium, Penicilium, Scedosporium, Scopulariopsis, Acremonium, and Trichoderma genera.

[List of diagnostic tests and procedures in leg ulcer]. / Osnovni dijagnosticki postupci kod bolesnika s venskim ulkusom.

Many factors contribute to the pathogenesis of leg ulcer. Most patients have venous leg ulcer due to chronic venous insufficiency. Less often, patients have arterial leg ulcer resulting from peripheral arterial occlusive disease, the most common cause of which is arteriosclerosis. Leg ulcer may be of a mixed arteriovenous origin. In diabetic patients, distal symmetric neuropathy and peripheral vascular disease are probably the most important etiologic factors in the development of diabetic leg ulcer. Other causes of chronic leg ulcers are hematologic diseases, autoimmune diseases, genetic defects, infectious diseases, primary skin diseases, cutaneous malignant diseases, use of some medications and therapeutic procedures, and numerous exogenous factors. Diagnosis of leg ulcer is based on medical history, inspection, palpation of skin temperature, palpation of arteries, fascia holes, presence and degree of edema, firm painful cords, and functional testing to assess peripheral occlusive arterial disease or identify superficial and deep venous reflux of the legs. Knowledge of differential diagnosis is essential for ensuring treatment success in patients with leg ulcer. There are many possible etiologic factors of leg ulcers and sometimes, clinical findings are similar. Additional testing should be performed, e.g., serologic testing such as blood count, C-reactive protein, HBA1c, erythrocyte sedimentation rate, differential blood count, total proteins, electrolytes, coagulation parameters, circulating immune complex, cryoglobulins, homocysteins, AT, PAI-1, APC resistance, proteins C and S, paraproteins, ANA, ENA, ANCA, dsDNA, antiphospholipid antibodies, urea, creatinine, blood lipids, vitamins and trace elements. Also, biopsy of the lesion for histopathology, direct immunofluorescence, bacteriology and mycology should be included. Other tests are Raynaud (cold stimulation) test and pathergy test. Device-based diagnostic testing should be performed for future clarification. Ankle brachial pressure index, color duplex sonography, plethysmography, MSCT and MR angiography, digital subtraction angiography, phlebography, angiography, x-ray, and capillaroscopy in lupus erythematosus are indicated. Except for bacteriologic analyses of wound biopsies, there is no test to provide specific information on the wound condition.

[Pemphigus chronicus vulgaris--case report]. / Pemphigus chronicus vulgaris--prikaz bolesnika.

Pemphigus vulgaris is a rare, chronic, autoimmune blistering skin disease of adulthood. In 50 percent of patients, mucous membrane erosions of the oral cavity are the presenting sign. Typically, patients develop flaccid blisters and erosions on the normal appearing skin and mucous membranes. Mucous membranes in other areas may also be involved. The disease is caused by IgG autoantibodies to the desmosomes inducing the loss of cell adhesion between keratinocytes, and subsequent intraepidermal blister formation. Antigens are desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) transmembrane glycoproteins. Desmoglein 3 is expressed in the lower portion of the epidermis. Alone, it is sufficient to keep mucosal surfaces intact. Desmoglein 1 is expressed more intensely in the superficial layers. Pemphigus vulgaris can be divided into two subgroups, the mucosal type and mucocutaneous type. The characteristic histologic finding is intraepidermal blister. Acantholytic keratinocytes as well as clusters of epidermal cells are seen in the blister cavity. Direct immunofluorescence examination (DIF) of perilesional skin shows a deposit of IgG, rarely IgA, and complement components (C3, C1q,C4) between the epidermal cells. The titers of circulating antibodies measured with indirect immunofluorescence examination (IIF) often correlate with the disease course. There are sporadic cases of pemphigus vulgaris associated with the use of drugs, in particular D-penicillamine and captopril. Pemphigus vulgaris has rarely evolved into pemphigus foliaceus, and vice versa. Very uncommon, pemphigus vulgaris or pemphigus foliaceus has been associated with bullous pemphigoid in the same patient. We present an unusual case of pemphigus vulgaris in an adult female patient.

Melanoma Development: Current Knowledge on Melanoma Pathogenesis.

The pathogenic features of melanomas include growth and amplification of atypical melanocytes associated with several features (self-sufficiency of growth factors, insensitivity to growth inhibitors, evasion of cellular apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion, and metastasis). These melanoma pathogenic events can be triggered by activating oncogenes or inactivating tumor-suppressor genes by means of molecular mechanisms such as dotted mutations, deletions, and translocations or epigenetic mechanisms such as microRNA expression and promoter methylation. In melanomas, an analysis of the gene aberrations in the genome has led to the discovery of the complex interaction of signaling pathways. Progression of melanomas also involves genetic instability and selective growth of cells with favorable mutations. Additional factors include genetic predisposition, mutagenesis, and suppressed host immune response. Some of the most important signaling pathways involved in the pathogenesis of melanoma are the MAPK, PI3K/PTEN/AKT, and MITF signaling pathways. Obtaining insight into the biology of melanocytes and pathogenesis of melanomas is important for the development of a targeted therapy (such as vemurafenib, dabrafenib, trametinib) as well as the immunotherapy (e.g. pembrolizumab, nivolumab, ipilimumab), which has enabled a substantial breakthrough in the treatment of patients with melanoma.

Erysipeloid--case report.

Erysipeloid is an acute, bacterial infection of traumatized skin in an individual who was in direct contact with meat or other animal products contaminated with a gram-positive bacillus Erysipelothrix rhusiopathiae. We present a case of a 50-year-old housewife whose hobby was fishing, with a reddish, tender patch on the fifth finger and dorsum of the left hand, which developed a week after she had sustained an injury while boning the fish. The patient was treated with orally administered penicillin V 1,500,000 IU t.i.d. for 7 days, with complete resolution.

Disseminated Hailey-Hailey disease treated with topical tacrolimus and oral erythromycin: Case report and review of the literature.

Hailey-Hailey disease is a rare autosomal dominant skin disorder that typically affects the intertriginous areas. The responsible defect has been identified in the gene named ATP2C1 on chromosome 3q21-24. We present a 50-year-old man with a 16-year history of blistering eruptions and positive familial history where this disease had appeared through four generations. The diagnosis was confirmed by histopathologic studies and negative immunofluorescence findings. A combination of topical tacrolimus therapy and oral erythromycin seemed to play a considerable part in this case, in which all of the lesions healed within 2 weeks.