Treatment of plaque-psoriasis in HIV-positive patients.

Psoriasis is a chronic inflammatory disease that can often accompany human immunodeficiency virus (HIV) epidemics. Development of psoriasis in HIV patients is correlated with a decrease in CD4+ count. Significant variability in the clinical presentation of psoriasis makes it a challenging disease to diagnose. Furthermore, associated immunodeficiency complicates standard treatment with immunosuppressive and biological therapy. Articles that match the terms psoriasis and HIV were searched in MEDLINE and Embase and selected based on their relevance. Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat HIV infection. In treating mild psoriasis in HIV-positive patients, topical agents combined with HAART are considered first-line therapy, followed by phototherapy. Second-line therapy includes oral retinoids, alone or combined. In treating challenging cases, apremilast has been used due to its lack of immunosuppressive effect. In case of progressive and refractory disease, limited data from studies suggest that immunosuppressive or biological therapy may be effective. Treatment of psoriasis in HIV patients remains a challenge, which is largely attributable to its complicated etiopathology and lack of an approved therapy option. In treating severe psoriasis, close collaboration with an infectious disease specialist is highly recommended. Further research is needed, preferably with an aim toward developing individualized therapy.

Poikilodermatous Mycosis Fungoides - Rare Entity, Different Treatment Modalities.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage MF with peculiar histological features. Poikiloderma occurs in many different clinical conditions, which makes a diagnostic procedure more complicated. PMF belongs to a group of MF variants with low risk of disease progression. We report a case of a 64-year-old woman, who presented with mottled skin aspect of erythema, poikilodermatous patches (hypopigmentation, hyperpigmentation, atrophy, and telangiectasia) on more than 80% of the body. Based on clinical, histopathological, and immunohistochemical findings, we established the diagnosis of PMF. Staging procedure determined stage IIA. As skin-directed therapy was the treatment of choice, the patient was successfully treated with psoralen-UVA (PUVA), nbUVB plus retinoid (Re-nbUVB), and PUVA plus retinoid (Re-PUVA), however, with rapid recurrence.

The Impact of Pyschological Stress on Acne.

Acne is one of the most common skin disorders. It is a multifactorial and complex disease, originating in the pilosebaceous follicle where a hereditary background, androgens, skin lipids, disorders of keratinization, inflammatory signaling, and regulatory neuropeptides seem to be mainly involved. Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction. A point to note is that there have been relatively few studies examining stress as a possible cause of acne or acne exacerbation; more studies have focused on stress and mental health problems occurring as a result of acne. In this review, we have tried to identify the underlying mechanisms that link stress to acne according to the latest scientific findings, and we summarize this perplexing connection. The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne. This bidirectional intimate relationship of the skin and the mind emphasizes the importance of a holistic and interdisciplinary approach to caring for patients with acne that involves not only dermatologists but also psychologists and psychiatrists.

Adverse Reaction to Cetuximab, an Epidermal Growth Factor Receptor Inhibitor.

Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities with dry, scaly, itchy skin (Figure 2). Furthermore, hair and nail changes gradually developed, culminating with trichomegaly (Figure 3) and paronychia (Figure 4). The patient was treated with oral antibiotics (tetracycline) and a combination of topical steroids with moisturizing emollients due to xerosis, without reduction of EGFRI therapy and with a very good response. Trichomegaly was regularly sniped with scissors. Nail fungal infection was ruled out by native examination and cultivation, so antiseptics and corticosteroid ointments were introduced for paronychia treatment. During the above-mentioned therapy, apart from skin manifestations, iatrogenic neutropenia grade IV occurred, with one febrile episode, and because of this, the dose of cytostatic drugs was reduced. After 10 months of therapy, progression of the disease occurred with lung metastases, so EGFRI therapy was discontinued and the patient was given second-line chemotherapy for metastatic colorectal carcinoma. This led to gradual resolution of all aforementioned cutaneous manifestations. Since the pathogenesis of skin side-effects due to EGFRI is not yet fully understood, there are no strict therapy protocols. Therapy is mainly based on clinical experience and follows the standard treatments for acne, rosacea, xerosis, paronychia, and effluvium. The therapeutic approach for papulopustular exanthema includes topical and systemic antibiotics for their antimicrobial as well as anti-inflammatory effect, sometimes in combination with topical steroids. Topical application of urea cream with K1 vitamin yielded positive results in skin-changes prevention during EGFRI therapy, especially with xerosis, eczema, and pruritus (6). Hair alterations in the form of effluvium are usually tolerable, and if needed a 2% minoxidil solution may be applied. Trichomegaly or abnormal eyelash growth can lead to serious complications, so ophthalmologic examination is needed. At the beginning of the growth, regular lash clipping may reduce possibility of corneal abrasion (7,8). Nail changes can just be a cosmetic problem (pigmentary changes, brittle nails), and in the occurrence of paronychia or onycholysis (of several or all nails) they result in high morbidity and impair daily activities. Nail management should be started as soon as possible because of slow nail growth and the relatively long half-life of EGFRI. Combination of topical iodide, corticosteroids, antibiotics, and antifungals with avoidance of nail traumatization will yield the best results (9). EGFRI are potentially life prolonging therapies, and our goal as dermatovenereologists is to provide optimal patient care and improve their quality of life in a multidisciplinary collaboration with oncologists, radiotherapists, and ophthalmologists.

Laser therapy of pigmented lesions: pro and contra.

Although frequently performed, laser removal of pigmented lesions still contains certain controversial issues. Epidermal pigmented lesions include solar lentigines, ephelides, café au lait macules and seborrheic keratoses. Dermal lesions include melanocytic nevi, blue nevi, drug induced hyperpigmentation and nevus of Ota and Ito. Some lesions exhibit both an epidermal and dermal component like Becker's nevus, postinflammatory hyperpigmentations, melasma and nevus spilus. Due to the wide absorption spectrum of melanin (500-1100 nm), several laser systems are effective in removal of pigmented lesions. These lasers include the pigmented lesion pulsed dye laser (510 nm), the Q-switched ruby laser (694 nm), the Q-switched alexandrite laser (755 nm) and the Q-switched Nd:YAG laser (1064 nm), which can be frequency-doubled to produce visible green light with a wavelength of 532 nm. The results of laser therapy are usually successful. However, there are still many controversies regarding the use of lasers in treating certain pigmented lesions. Actually, the essential question in removing pigmented lesions with lasers is whether the lesion has atypical features or has a malignant potential. Dermoscopy, used as a routine first-level diagnostic technique, is helpful in most cases. If there is any doubt whether the lesion is benign, then a biopsy for histologic evaluation is obligatory.

Antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriasis patients.

The aim of the study was to investigate the antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriatic patients, and to compare it with a control group of psoriatics treated with local corticosteroid therapy. The study included 60 psoriasis patients, 30 of them allocated to PUVA therapy and local corticosteroid each. Immunohistochemical methods of staining with Ki-67, F-8 and bcl-2 antibodies were used to determine proliferative keratinocyte count, to visualize the number of blood vessels in the dermis, and to determine the number of cells exhibiting expression of the antiapoptotic oncoprotein bcl-2, respectively. In all study patients, the values of Ki-67, F-8, bcl-2 and PUVA score were recorded pre- and at six weeks post-therapeutically. Study results showed a statistically significant decrease in the epidermal proliferative keratinocyte count and dermal number of blood vessels after both therapeutic modalities (p < 0.001 both). The value of bcl-2 showed a statistically significant increase in the group of patients treated with PUVA therapy (p = 0.001) and an increase in the control group, demonstrating enhanced keratinocyte apoptosis after treatment. Accordingly, study results demonstrated the antiproliferative, antiangiogenic and apoptotic effect of both PUVA and local corticosteroids. These very mechanisms appear to play a key role in the action of most antipsoriatic therapies.

Treatment of childhood psoriasis.

Psoriasis is a common disease in children and adolescents. Because of the chronic course of the disease, appropriate choice of therapy in particular stage of the disease, so-called rotation therapy, is of paramount importance. This article provides a review of therapeutic options for childhood psoriasis. Local therapy for psoriasis in children consists of corticosteroid preparations, calcipotriol, tars and dithranol, local retinoids, and local immunomodulators. Phototherapy (narrow band UVB, photochemotherapy PUVA baths) is now a part of psoriasis therapy in children. Systemic therapy retinoids (acitretin) methotrexate, cyclosporine is only used in severe forms of the disease such as erythrodermic, pustular and arthritic psoriasis. All these therapeutic options can be used as monotherapy or in various combinations.

Phototherapy in pediatric patients.

The treatment of children with psoriasis, atopic dermatitis (AD), pityriasis lichenoides, and scleroderma poses a therapeutic problem because all therapeutic options are associated with numerous side effects. Therefore ultraviolet A and B (UVA and UVB) phototherapy is presented as a possible alternative to some of these therapies, primarily topical and systemic corticosteroids, in children. Our results in treating children with phototherapy and psoralen plus UVA (PUVA) bath phototherapy over the past 5 years are reported. UVB therapy (TL01) was used in 20 psoriatic children (6 boys, 14 girls; ages 6-14 years) during the stage of disease exacerbation and in 9 children (3 boys, 6 girls; ages 8-16 years) with pityriasis lichenoides. Combined UVA/UVB phototherapy was applied in 21 AD children (7 boys, 14 girls; ages 4-15 years). Photochemotherapy with local application of a PUVA bath was used in six children (2 boys, 4 girls; ages 9-16 years) with circumscribed scleroderma and in one girl with systemic scleroderma. All children received short courses of phototherapy with either no maintenance or short maintenance. All three therapeutic protocols resulted in a certain degree of improvement in most of the study patients. None of the patients exhibited any early phototherapy side effects. We conclude that phototherapy and PUVA bath are valuable and safe therapeutic options for selected children who do not respond to other treatments.