Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

Neutrophilic urticarial dermatosis and Sweet-like neutrophilic dermatosis: under-recognized neutrophilic dermatoses in lupus erythematosus.

Background/Objectives Neutrophilic dermatoses can be associated with autoimmune connective tissue diseases such as systemic lupus erythematosus (SLE). We analyzed clinical and histological features of neutrophilic urticarial dermatosis (NUD) and Sweet-like neutrophilic dermatosis (SLND)-the most recently delineated entities of the neutrophilic dermatoses. Methods We retrieved database medical records of patients with SLE whose skin biopsy demonstrated a neutrophilic-predominant infiltrate of the skin, and included those whose biopsies revealed findings of SLND or NUD. Results SLND skin lesions lasted longer than those of NUD and were localized to sun-exposed areas. All NUD cases resolved within one week either spontaneously or with treatment such as antihistamines, but SLND skin lesions lasted longer than one week; prednisone was used in four of these five patients. All NUD cases were found in existing SLE patients and were not associated with systemic signs of flare-up of SLE. However, 80% of SLND cases experienced flare-up of SLE; and in 60%, SLND developed concomitantly with SLE as a presenting sign. Conclusion Different clinical courses and relationships with SLE suggest that NUD and SLND have different pathogeneses for neutrophilic inflammatory reactions.

First case of anaphylaxis after botulinum toxin type A injection.

Botulinum toxin type A (BTA) (also known as onabotulinum toxin A) injection is widely used in the field of cosmetic dermatology. Although a few adverse events related to intramuscular BTA injection have been reported, no life-threatening adverse reaction has been documented to date. We report a case of anaphylaxis induced by intramuscular BTA injection into the masseter muscles of a 35-year-old woman. She had previously received injections of the identical BTA product into the same muscles without incident. However, during the reported procedure, symptoms suggestive of angio-oedema and anaphylaxis developed about 5 min after BTA injection. Intramuscular epinephrine was used to manage the reaction. Following this, the patient was found to have an elevated total serum IgE level. We could not perform testing with BTA because of the risk of triggering another episode of anaphylaxis; however, intradermal tests using the identical sterile saline and patch test using the topical anaesthetic cream both showed negative results, thus we strongly suspect BTA as being the cause of anaphylaxis in this case.

Expression of programmed death-1 in cutaneous extranodal natural killer/T-cell lymphoma and its effect on clinical findings and biological behaviour.

BACKGROUND: Recent studies have evaluated the expression of programmed death-1 (PD-1) and its prognostic value in malignant T-cell lymphomas. OBJECTIVES: This study investigated whether the positivity of PD-1 was associated with the clinical characteristics of cutaneous extranodal NK/T-cell lymphoma (ENKTL) and evaluated its effects on survival outcomes. METHODS: Forty-one patients with cutaneous ENKTL were included. Clinical features and survival outcomes were analysed according to the positivity of PD-1. RESULTS: There was no significant difference between primary cutaneous ENKTL and secondary cutaneous ENKTL in the expression of PD-1. The degree of disease dissemination was not affected by the positivity of PD-1. Higher positivity for PD-1 was associated with lesions presenting erythematous to purpuric patches that are mainly composed of small tumour cells. Cutaneous ENKTL presenting nodular lesions had a significantly lower number of PD-1-positive infiltrating cells than those with other clinical morphologies. There was no significant effect of PD-1 expression on outcomes such as overall and progression-free survival. LIMITATIONS: This study used a retrospective design and had a small sample size. CONCLUSION: Higher PD-1 positivity is associated with small-cell-predominant cutaneous ENKTL. However, PD-1 expression has no prognostic value in cutaneous ENKTL.

Radotinib-induced lentiginosis: a report of an adverse cutaneous reaction associated with a tyrosine kinase inhibitor.

Tyrosine kinase inhibitors (TKIs) are associated with various adverse cutaneous reactions, including pigmentary changes. Radotinib is a novel and selective BCR-ABL1 TKI, which has shown activity and safety in the treatment of patients with chronic myeloid leukaemia resistant or intolerant to imatinib. A 69-year-old Korean man presented with lentiginosis after taking radotinib for 6 months. On histopathological examination, the numbers of melanocytes and melanin pigment were found to be increased due to c-KIT activation, consequently upregulating microphthalmia-associated transcription factor. This finding is in contrast to previous reports analysing the mechanisms of previously reported tyrosine kinase inhibitors inhibiting c-KIT.

A combination of excimer laser treatment and topical tacrolimus is more effective in treating vitiligo than either therapy alone for the initial 6 months, but not thereafter.

BACKGROUND: There are insufficient data on the long-term outcome of a combination therapy that comprises phototherapy and topical administration of tacrolimus. AIM: To evaluate the clinical efficacy according to the duration of treatment and in vitro results of a combination therapy involving topical tacrolimus and an excimer laser in the treatment of vitiligo. METHODS: In total, 276 patients with nonsegmental vitiligo were treated with an excimer laser twice weekly, or with tacrolimus ointment twice daily, or both. The melanin contents and levels of melanogenic enzymes were measured in cultured human melanocytes treated with tacrolimus and/or excimer laser. RESULTS: After adjusting for potential confounders, the combination of tacrolimus plus excimer laser was significantly more effective than either tacrolimus or excimer laser alone (P < 0.001 and P < 0.01, respectively) for the first 6 months. However, this superiority was not observed after the initial 6 months of treatment. In vitro, the combination of tacrolimus plus excimer laser led to a higher level of melanogenesis than with either treatment alone. CONCLUSIONS: A combination treatment with topical tacrolimus and an excimer laser may be useful as an induction therapy for up to 6 months, but continuation of this therapy for > 6 months might not provide a better final outcome than monotherapy.

Secondary cutaneous lymphoma: comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage.

BACKGROUND: The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. OBJECTIVES: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. MATERIALS AND METHODS: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. RESULTS: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. CONCLUSIONS: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Efficacy and safety of injection with poly-L-lactic acid compared with hyaluronic acid for correction of nasolabial fold: a randomized, evaluator-blinded, comparative study.

BACKGROUND: Hyaluronic acid (HA) fillers and poly-L-lactic acid (PLA) fillers are frequently used to correct facial wrinkles. AIM: To compare the efficacy and safety of a novel injectable poly-L-lactic acid (PLA) filler and a well-studied biphasic HA filler for the treatment of moderate to severe nasolabial folds. METHODS: In this multicentre, randomized, evaluator-blinded, comparative study, subjects were randomized for injections with PLA or HA into both nasolabial folds. Efficacy was determined by calculating the change in Wrinkle Severity Rating Scale (WSRS) relative to baseline. Local safety was assessed by reported adverse events. RESULTS: At week 24, mean improvement in WSRS from baseline was 2.09 ± 0.68 for the PLA side and 1.54 ± 0.65 for the HA side. Both injections were well tolerated, and the adverse reactions were mild and transient in most cases. CONCLUSIONS: PLA provides noninferior efficacy compared with HA 6 months after being used to treat moderate to severe nasolabial folds.

A case of xanthoma disseminatum: evaluation and monitoring by 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Xanthoma disseminatum (XD) is a rare benign histiocytic disorder with extensive mucocutaneous xanthomas that often involves other sites such as the central nervous system (CNS), respiratory tract and abdominal organs. Evaluation of the extent of disease is important because lesions in critical locations may increase morbidity and mortality. However, there are no well-established tools for the evaluation and monitoring of XD. Here, we report a case of XD in a 21-year-old male patient showing skin, mucous membrane, CNS and internal organ involvement. In this case, (18) F-fluorodeoxyglucose positron emission tomography/computed tomography was useful in detecting the extent of the disease and in estimating the therapeutic response.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

BACKGROUND: Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. OBJECTIVES: To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. METHODS: Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. RESULTS: There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. CONCLUSIONS: The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites.

Paediatric cutaneous lymphoma in Korea: a retrospective study at a single institution.

BACKGROUND: The clinical features and incidences of cutaneous lymphoma (CL) differ by ethnicity and age. However, there is to our knowledge no study to show characteristics and distribution of paediatric CL in Asian population. OBJECTIVE: The aim of this study was to investigate distinctive clinicopathological features of CL in paediatric population, particularly in Korea. METHODS: We conducted a clinicopathological review of 41 paediatric cases with CL, diagnosed at Asan Medical Center from January 1990 to December 2012. The clinical records, haematoxylin & eosin-stained slides and immunohistochemical stains from paediatric patients with CL were analyzed. In addition, the results in this present paediatric group were compared with previously reported studies in the Korean all-ages group and Western paediatric group. RESULTS: Lymphomatoid papulosis was more common in the present paediatric group than in the all-ages group (34.5% vs. 9.4%) and Western paediatric group (34.5% vs. 17.7%). Mycosis fungoides, the most common cutaneous lymphoma in the all-ages group and Western paediatric group, is the second most common subtype in this study. Three of nine paediatric mycosis fungoides patients (33%) have the follicular variant. Compared with all-ages group, B-lmphoblastic lymphoma was relatively higher incidence (10.3% vs. 1%) and NK-/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma was relatively in lower proportions in the paediatric group. CONCLUSION: The clinical features and distribution of paediatric CL in our study suggest that CL of Asian childhood is quite different from that of adulthood and Western childhood.

Histopathological study of the treatment of melasma lesions using a low-fluence Q-switched 1064-nm neodymium:yttrium-aluminium-garnet laser.

The low-fluence 1064-nm Q-switched neodymium:yttrium-aluminium-garnet (QSNY) laser is a widely used treatment for melasma in East Asia, although its mechanism of action is unclear. The aim of this study was to elucidate the mechanism of action of the QSNY laser. We performed a histopathological study on eight Korean women who had considerable improvement in their melasma lesions after a series of low-fluence QSNY laser treatments. Compared with nonlesional skin, samples from melasma lesions showed increased reactivity in melanin (Fontana-Masson staining) and in melanogenesis-associated proteins, including α-melanocyte-stimulating hormone, tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, nerve growth factor and stem cell factor. After laser treatment, the melasma skin showed a decrease in the number of melanosomes and reduced expression of melanogenesis-associated proteins. Expression levels of the melanogenic proteins were reduced after laser treatment, although the number of melanocytes was unchanged even in hypopigmented areas. Based on these results, we believe that repeated application of low thermal energy via QSNY laser may result in damage to melanocytes and long-lasting hypopigmentation.

RimabotulinumtoxinB vs. onabotulinumtoxinA for the treatment of forehead lines: an evaluator-blind, randomized, pilot study.

BACKGROUND: Optimum dose ratios of rimabotulinumtoxinB (BTX-B) and onabotulinumtoxinA (BTX-A) have not been determined for forehead wrinkles. OBJECTIVE: To compare the efficacy and safety of BTX-B and BTX-A for the treatment of forehead lines. METHODS: Twenty-two women (mean age, 40 years) with symmetrical moderate to severe forehead lines were randomized to receive single intramuscular injections of BTX-A and BTX-B on either side of the forehead, at a potency ratio of 1 : 70 or 1 : 100. Subjects were followed-up for 16 weeks. Four physicians evaluated patients' photographs according to the 4-point Facial Wrinkling Grade (FWG). Clinical Improvement Scale (CIS) was calculated by subtracting FWG score at each visit from that at baseline. Patient satisfaction scores and adverse events were also recorded. RESULTS: Both BTX-A and BTX-B were effective for the treatment of forehead lines. At both potency ratios, BTX-A had a longer duration of action than BTX-B, while BTX-B led to faster improvement than BTX-A. There was no significant difference in CIS between 700 U and 1000 U BTX-B treatments. Adverse effects were mild and transient. CONCLUSION: Both BTX-A and BTX-B were effective and well tolerated for the treatment of forehead wrinkles at potency ratios of 1 : 70 and 1 : 100.

Synchronous infection with Mycobacterium chelonae and Paecilomyces in a heart transplant patient.

A 41-year-old male who was 3 years status post heart transplant presented with a 3-month history of painful erythematous nodules and ulcers on his lower legs and right hand. First, Mycobacterium chelonae infection was revealed through several biopsies with molecular sequence analysis, and combination treatment, including clarithromycin, was started. During the treatment, lesions of the legs showed an improvement, but a fluctuant erythematous nodule on the thumb did not respond. Repetitive biopsy from the thumb ultimately identified Paecilomyces species and the patient was treated with itraconazole and terbinafine sequentially. Our case is the first report, to our knowledge, of synchronous infection with non-tuberculous mycobacteria (NTM) and Paecilomyces in a solid organ transplant recipient. Our findings highlight the importance of recognizing cutaneous NTM infections or deep mycoses, as well as the importance of choosing an appropriate treatment.

Expression of neuropeptides and their degrading enzymes in ACD.

BACKGROUND: Sensory neuropeptides such as neurokinin A or substance P modulate skin and immune cells the functions of neurokinin receptor activation during neurogenic inflammation. Zinc metalloproteases, such as neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), effectively control the bioavailability of these neuropeptide mediators, which are released from sensory nerves, immune and skin cells during cutaneous responses to endogenous or exogenous noxious stimuli. Recently, studies have suggested that neuropeptides are one of the major pathogenetic fact in many dermatoses, such as allergic contact dermatitis (ACD), atopic dermatitis and psoriasis. AIM: To investigate the expression of major neuropeptides, SP and its degrading enzymes such as NEP and ACE, in the lesions of ACD. METHODS: A skin biopsy was obtained from 10 patients with ACD. We analysed the expression of these molecules by immunohistochemical staining, confocal laser scanning microscopy, western blotting and reverse transcription PCR. RESULTS: There was a significant increase in expression of SP in keratinocytes from ACD lesions compared with those in control skin. There was also increased expression of ACE but not NEP in ACD. CONCLUSION: Neuropeptides and their degrading enzymes, particularly SP and ACE, have a significant role in the pathogenesis of ACD.

Monoclonal antibodies in the analysis of fibronectin isoforms generated by alternative splicing of mRNA precursors in normal and transformed human cells.

Recent results showing that a single fibronectin gene can give rise to several different mRNAs by alternative splicing have offered an explanation for fibronectin polymorphism. Here we report on monoclonal antibodies that show specificity for a fibronectin segment (ED) that can be included or omitted from the molecule depending on the pattern of splicing of the mRNA precursors. Using these monoclonals, we have quantitatively analyzed the expression of the ED sequence in human fibronectin from different sources. The results demonstrated that, at the protein level, the ED segment is not expressed in plasma fibronectin and that, in fibronectin from the tissue culture medium of tumor-derived or simian virus-40-transformed human cells, the percentage of fibronectin molecules containing the ED segment is about 10 times higher than in fibronectin from normal human fibroblasts. These results suggest that in malignant cells the mechanisms that regulate the splicing of mRNA precursors are altered.

Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib.

BACKGROUND: The multitargeted kinase inhibitors sorafenib and sunitinib have improved treatment of solid tumours including renal cell carcinoma and hepatocellular carcinoma by offering better clinical responses. However, sorafenib and sunitinib are commonly associated with cutaneous toxicity. OBJECTIVES: We conducted this study to make a clinical assessment of the cutaneous toxicities induced by the oral multitargeted kinase inhibitors sorafenib and sunitinib. METHODS: Retrospectively, we reviewed medical records of patients receiving multitargeted kinase inhibitors, including 109 patients on sorafenib for the treatment of renal cell carcinoma or hepatocellular carcinoma and 119 patients receiving sunitinib for treatment of renal cell carcinoma or a gastrointestinal stromal tumour. Clinical data on cutaneous toxicities were collated. We describe the incidences and intensities of toxicities, and analyse the data statistically. RESULTS: The most common cutaneous toxicity was hand-and-foot skin reaction (HFSR). Other cutaneous toxicities included alopecia, stomatitis, skin discoloration (hair or face), subungual splinter haemorrhage, facial swelling, facial erythema and xerosis. HFSR and severe stomatitis required therapy modifications to relieve symptoms, but other cutaneous toxicities did not affect treatment course. HFSR was observed in 48% of patients treated with sorafenib and 36% of those treated with sunitinib. Median time to onset was 18.4 days in patients receiving sorafenib and 32.4 days in those receiving sunitinib. HFSR and stomatitis were early symptoms compared with other cutaneous toxicities. Patients with severe HFSR were likely to develop the symptoms at early phases of therapy. A significant correlation between the severity of HFSR and development of alopecia and stomatitis was found. CONCLUSIONS: Multitargeted kinase inhibitors are associated with a significant risk of various cutaneous adverse events. HFSR is the commonest and most serious cutaneous toxicity in patients treated with these drugs.