Andac Salman

Efficacy, safety and drug survival of conventional agents in pediatric psoriasis: A multicenter, cohort study

The data on long‐term efficacy, safety and drug survival rates of conventional systemic therapeutics in pediatric psoriasis is lacking. The primary aim of this study is to investigate acitretin, methotrexate, cyclosporin efficacy, safety and drug survival rates in pediatric patients as well as predictors of drug survival. This is a multicenter study including 289 pediatric cases being treated with acitretin, methotrexate and cyclosporin in four academic referral centers. Efficacy, adverse events, reasons for discontinuation, 1, 2‐ and 3‐year drug survival rates, and determinants of drug survival were analyzed. A 75% reduction of Psoriasis Area and Severity Index score or better response rate was obtained in 47.5%, 34.1% and 40% of the patients who were treated with acitretin, methotrexate and cyclosporin, respectively. One‐year drug survival rates for acitretin, methotrexate and cyclosporin were 36.3%, 21.1% and 15.1%, respectively. The most significant determinant of drug survival, which diminished over time, was treatment response whereas arthritis, body mass index and sex had no influence. Although all three medications are effective and relatively safe in children, drug survival rates are low due to safety concerns at this age group. Effective disease control through their rational use can be expected to improve survival rates.

Panniculitis in juvenile dermatomyositis: Report of a case and review of the published work.

We report a 15‐year‐old girl who presented with indurated, subcutaneous nodules in addition to classical findings of juvenile dermatomyositis. Histopathological examination confirmed the diagnosis of panniculitis associated with juvenile dermatomyositis. Considering that panniculitis is a rare cutaneous manifestation of juvenile dermatomyositis, we present a patient with a brief review of the published work to highlight the importance of keeping juvenile dermatomyositis in mind among the etiologies of pediatric panniculitis.

Infliximab-induced cutaneous eruption resembling pityriasis rubra pilaris in a patient with Takayasu's arteritis

Dear Editor, Infliximab is a widely used chimeric, monoclonal antibody for the treatment of various chronic, inflammatory, immune-mediated diseases. It has been associated with several cutaneous toxicities (Hawryluk, Linskey, Duncan, & Nazarian, 2012). Herein, we report a patient with Takayasu’s arteritis in whom a cutaneous eruption clinically mimicking pityriasis rubra pilaris (PRP) developed soon after starting infliximab treatment. A 53-year-old woman presented with a 4-week-history of generalized eruption. Her medical history was unremarkable except for Takayasu’s arteritis for 18 years. She was on treatment with infliximab and isoniazid for 6 weeks along with methylprednisolone, acetylsalicyclic acid, pantoprazole, calcium, and vitamin D for the last 4 years. Shortly after the second cycle of infliximab, a mild, erythematous, scaly rash developed on the scalp which rapidly spreaded to the trunk and extremities. No personal or family history of papulosquamous diseases was present. Dermatological examination revealed orange-tosalmon-colored, scaly patches with islands of sparing and follicular, erythematous papules on the trunk and extremities reminiscent of PRP (Figure 1a–c). Erythema with fine scales on the scalp and face was also evident. Two punch biopsies were obtained from erythematous patches and follicular papules. Histopathological examination showed hyperkeratosis and focal parakeratosis, necrotic keratinocytes, vacuolar degeneration and mild acanthosis in the epidermis and extravasated erythrocytes and superficial perivascular mononuclear infiltration in dermis (Figure 2). Laboratory tests including complete blood count, hepatic transaminases, renal function tests, and anti-HIV showed no abnormalities. The eruption gradually resolved spontaneously without any intervention, probably due to decreasing serum levels of infliximab inbetween infusions (Figure 1d–f). Based on the clinicopathological findings and the temporal relationship between the eruption and infliximab treatment, a diagnosis of infliximab-induced cutaneous eruption resembling PRP was made. Considering the severity of initial eruption and ethical concerns, no rechallenge was planned and infliximab was discontinued which led to further improvement of her skin reaction. The patient is currently being treated with leflunomide. Infliximab, a TNF-alpha inhibitor, is an effective treatment alternative in numerous disorders including rheumatoid arthritis, Crohn’s disease and psoriasis. In addition to infusion reactions, a wide variety of cutaneous side effects including non-specific maculopapular rash and paradoxical onset or exacerbation of psoriasis, sarcoidosis or hidradenitis suppurativa have been reported during infliximab treatment (Hawryluk et al., 2012; Mocci, Marzo, Papa, Armuzzi, & Guidi, 2013). Cutaneous eruption resembling PRP has been reported in association with other drugs including sorafenib, imatinib, ponatinib and telaprevir (Jack, Mauro, & Ehst, 2013; Paz, Querfeld, & Shea, 2011; Plana, Carrascosa, Vilavella, & Ferrandiz, 2013; Stalling, Vu, & English, 2012). However, to our knowledge, infliximab-induced cutaneous eruption suggestive of PRP or paradoxical development of PRP have not been reported before. Besides, off-label and efficacious use of infliximab has been repeatedly reported in treatment-resistant, severe PRP (Garcovich, Di Giampetruzzi, Antonelli, Garcovich, & Didona, 2010; Petrof, Almaani, Archer, Griffiths, & Smith, 2013; Wollina, 2012). In the present case, clinical differential diagnosis encompassed infliximab-induced cutaneous eruption resembling PRP and infliximabinduced paradoxical PRP. Clinical characteristics suggestive of PRP in our patient were orange-to-red-colored erythematous patches with fine scale and areas of sparing, and follicular papular lesions. However, the presence of necrotic keratinocytes and prominent vacuolar degeneration on the histopathological examination supported a diagnosis of drug-induced cutaneous eruption over PRP. Switching to another anti-TNF agent was not attempted in our patient due to a possible class effect. In conclusion, although infliximab holds a promising potential in treatment of recalcitrant PRP, it may induce cutaneous eruptions clinically simulating PRP as well. Thus, all patients presenting with PRP-like clinical features should be asked for the use of infliximab in addition to other drugs causing PRP-like drug eruptions.

Facial discoid dermatosis: A further case of a novel entity.

MCNS. A 48-year-old man who had suffered from MCNS since the age of 23 years was referred to our hospital due to the excessive hair loss throughout the body. Although he had been treated with several types of medical treatments including oral prednisolone, the renal dysfunction associated with MCNS had never been completely recovered. Approximately nine months before his visit to our clinic, he noticed active hair loss throughout the body. Seven months after the beginning of hair loss, MCNS had relapsed again. Clinical examination showed complete hair loss throughout the body, including scalp, body and extremities (Fig. 1a). Blood test showed no thyroid dysfunction and negative anti-nuclear antibodies. Immunoglobulin E (IgE) showed higher values of 910 IU/mL. A histological examination of skin specimens from the scalp revealed increased percentage of telogen HF (Fig. 1b) and inflammatory cell infiltrations composed of lymphocytes and histiocytes around the HF bulb (Fig. 1c–e). Taken together, we diagnosed this case as alopecia universalis. Renal dysfunction was gradually improved by oral prednisolone therapy. Minimal change nephrotic syndrome is a common nephrotic disease in both children and adult, and is highly steroid responsive. High frequency of relapses of this disease is also well known. However, the pathogenesis of MCNS is still largely unknown. Histopathologically, there are no remarkable changes in the kidney. Similar with AA, T lymphocytes and their cytokine are reported to be involved in the pathogenesis of MCNS. Interestingly, MCNS is reported to be associated with allergic diseases and elevated serum IgE levels. Shao et al. also reported that “enzymatic degradation of IgE may remove the anionic charge on the glomerular filtration barrier, which is generated by the sulfate groups of heparan sulfate” (p. 266). Furthermore, the authors suggested the possibility that mast cells (MC) which express heparanase can degrade heparan sulfate in a subendothelial extracellular matrix and this may offer us a possible mechanism for the association between high serum IgE, MC and proteinuria. In line with this, IgE-dependent histamine-releasing factor is overexpressed in the nephrotic phase of MCNS. In fact, this patient has higher IgE levels, and a lot of MC can be detected around the HF (Fig. 1f–h). Intriguingly, perifollicular MC has recently been reported to play an important role in the development of AA. Although we could not detect direct evidence that MCNS induced alopecia universalis, our results may suggest that both diseases have similar pathogenesis.

Prevalence of obesity in paediatric psoriasis and its impact on disease severity and progression

The current literature suggests there is a possible connection between paediatric psoriasis and obesity. However, there is a paucity of research on the influence of increased adiposity on the severity of paediatric psoriasis and disease progression. We aimed to compare the prevalence of being overweight or obese in paediatric psoriasis patients and controls and assess the potential impact of being overweight/obese on disease severity and progression of disease.

Another adverse effect of vemurafenib: Gingival hyperplasia.

Dear Editor, Vemurafenib is a small-molecule inhibitor approved in the treatment of BRAF V600 mutation-positive metastatic melanoma. This targeted drug has notoriously been associated with a unique spectrum of skin toxicities which has been reported to be seen in all treated patients in a prospective study. Among these are maculopapular rash, photosensitivity, plantar hyperkeratosis, hand–foot reaction, keratosis pilaris-like reaction, verrucous papillomas and malignancies, notably keratoacanthoma/squamous cell carcinoma. To the best of our knowledge, gingival hyperplasia related to vemurafenib has only once been reported in a patient with metastatic melanoma showing progression despite vemurafenib treatment. Here, we report a similar observation, further underscoring gingival hyperplasia as a possible adverse effect of vemurafenib. A 33-year-old man with metastatic melanoma showing BRAF V600 mutation was referred to our clinic. He had stable disease under vemurafenib treatment for 6 months. During the course of vemurafenib treatment, mild alopecia, plantar hyperkeratosis and keratosis pilaris-like folliculocentric eruption were noted. In addition, he complained of new-onset painful swelling of the gums for 1 month. Oral examination revealed slightly frambesiform gingival hyperplasia accompanied by superficial erosions, more pronounced on the marginal and attached parts of the maxillary gingiva (Fig. 1). Due to decreased oral intake, vemurafenib treatment was interrupted for 1 week, leading to modest amelioration of the oral symptoms. Based on the absence of concomitant medications and medical conditions known to be associated with gingival hyperplasia and temporal relationship, gingival hyperplasia was attributed to vemurafenib. At the final examination, a combination treatment of vemurafenib and cobimetinib was planned. The cutaneous side-effects of vemurafenib have tentatively been explained by the paradoxical activation of retrovirusassociated sequence (RAS), which is an upstream component of the RAS–RAF–mitogen-activated protein kinase kinase– extracellular signal-regulated kinase intracellular signaling pathway, and thus, have been designated as “RASopathic”. Supporting this theory, many cutaneous adverse effects of vemurafenib, such as keratosis pilaris and plantar hyperkeratosis, coincide with the spectrum of cutaneous findings seen within the context of the inherited “RASopathies”. Mangold and colleagues argued that gingival hyperplasia may be another RASopathic adverse effect of vemurafenib. We hypothesize that another molecular pathomechanism may possibly account for the vemurafenib-associated gingival changes. Secondary resistance to vemurafenib, which is known to develop in almost all patients after a median interval of approximately 6 months, may involve the activation of an extrinsic pathway, called PI3K–AKT–mammalian target of rapamycin (mTOR). Interestingly, gingival hyperplasia is an important manifestation of both tuberous sclerosis complex and Cowden syndrome,

Atypical presentations of eosinophilic fasciitis.

Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia.

Mesalazine-induced bullous fixed drug eruption

Department of Dermatology, Marmara University School of Medicine, Istanbul, Turkey Department of Gastroenterology, Marmara University School of Medicine, Istanbul, Turkey Department of Dermatology, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain Correspondence Andac Salman, Department of Dermatology, Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Dermatoloji Anabilim Dali Fevzi Cakmak Mah, Mimar Sinan Caddesi No. 41, 34899 Pendik, Istanbul, Turkey. Email: asalmanitf@gmail.com; ac.salman@marmara.edu.tr

Acquired progressive lymphangioma: Case report with partial response to imiquimod 5% cream

Acquired progressive lymphangioma (APL), or benign lymphangioendothelioma, is an unusual entity derived from vascular structures. Clinically and histopathologically it may resemble Kaposis sarcoma and well‐differentiated angiosarcoma, causing a diagnostic problem. We report an individual with APL initially diagnosed with Kaposis sarcoma who underwent unnecessary laboratory testing. Imiquimod 5% cream stopped the progression of the lesion. Awareness of this rare entity may prevent patients from undergoing excessive testing. Imiquimod may be used as a safe, effective treatment option.

Autoimmun-Progesteron-Dermatitis, die ein fixes Arzneimittelexanthem vortäuscht

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