Stevens‐Johnson syndrome and toxic epidermal necrolysis associated with the use of macrolide antibiotics: a review of published cases

Macrolides are one of the most commonly prescribed antibiotics. In several studies, their use was associated with the occurrence of Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This review aimed to explore and summarize available cases of SJS/TEN suspected to be associated with the use of macrolide antibiotics reported in the literature. Electronic searches were conducted in PubMed/MEDLINE, Web of Science, Scopus, and Serbian Citation Index (SCIndeks). Twenty‐five publications describing a total of 27 patients were included. Cases of SJS/TEN which satisfied inclusion criteria were found for azithromycin (n = 11), clarithromycin (n = 7), erythromycin (n = 5), roxithromycin (n = 2), and telithromycin (n = 2). The age of the patients ranged from 2 to 77 years (median: 29 years). There were 14 female (51.9%) and 13 male (48.1%) patients. SJS was diagnosed in 16 patients (59.3%), TEN in 10 patients (37.0%), and SJS/TEN overlap in one patient (3.7%). Time to onset of the first symptoms ranged from 1 to 14 days (median: 3 days). All patients received some form of supportive and symptomatic care. Systemic corticosteroids were reported to be administered in 12 patients (44.4%) and intravenous immunoglobulin in five patients (18.5%). Three patients (11.1%) died. Considering that SJS/TEN is a severe and potentially life‐threatening reaction, physicians should be aware that they could be adverse effects of macrolide antibiotics and keep in mind that prompt recognition of SJS/TEN and discontinuation of the culprit drug in combination with supportive care is essential.     

Risk of subsequent cutaneous malignancy in patients with prior melanoma: a systematic review and meta‐analysis

Melanoma patients are known to be at risk of developing multiple cutaneous (pre‐) malignancies, however, the exact dimensions of these risks are unknown. In this meta‐analysis, risks of developing a melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) after a melanoma were investigated. An extensive systematic literature search was conducted (last performed on 18 January 2012). Studies reporting risks, i.e. proportions, standardized incidence ratios (SIR) and cumulative risks (CRs) were included. Fifty, of 233 fully read articles, met selection criteria. Two independent reviewers extracted data on study characteristics and risks measurements. Random‐effects meta‐analyses were used to pool the risk estimates for the three tumour combinations. In melanoma patients, pooled proportions for a subsequent melanoma, BCC or SCC were respectively 3.8% (n = 47), 2.8% (n = 5) and 1.0% (n = 6). The pooled SIRs for a subsequent melanoma, BCC or SCC in melanoma patients were respectively 10.4 (n = 12), 4.6 (n = 2) and 2.8 (n = 2). Mean 20‐year CRs of a subsequent melanoma, BCC or SCC in melanoma patients were respectively 5.4% (n = 3), 14.0% (n = 1) and 4.0% (n = 1). Subgroup analyses showed substantial differences in reported risks between continents and study design. In conclusion, a history of a prior melanoma is a strong predictor for development of a subsequent melanoma (approximately 10‐fold increased risk) and to a lesser extent BCC or SCC. This information could serve as information for health care systems. Further, secondary prevention seems pivotal in this patient group.     

Capillary‐Venous Malformation in the Lower Limb

Regional capillary malformation of a lower extremity is associated with the overgrowth of bone or soft tissue in several disorders, most commonly Klippel–Trenaunay syndrome and Parkes Weber syndrome. We have observed a subset of patients with a capillary malformation of the leg, minor growth disturbance, and prominent veins. The objective of the current study is to describe a series of patients with regional capillary malformation of the lower extremity in association with phlebectasia. This is a retrospective series of 17 patients diagnosed with capillary‐venous malformation of the lower extremity. We excluded patients with clinical or radiographic evidence of lymphatic or arteriovenous malformation. Age, presentation, associated features, radiographic findings, and management were documented. In most patients the capillary malformation covered a large area without sharply demarcated borders. Four patients had one or more discrete, well‐defined capillary stains involving less than 5% of the total surface area of the affected lower limb. Prominent veins were most common in the popliteal fossa and on the knee and dorsal foot. Approximately two‐thirds of patients had a leg length discrepancy, with the affected leg being longer (n = 6) or shorter (n = 4); in many the affected leg was also slightly larger (n = 8) or smaller (n = 4) in girth. Radiographic imaging showed dilatation of superficial (n = 16), muscular (n = 9), and deep veins (n = 6). We characterize a subset of patients with regional capillary‐venous malformation of the lower extremity with prominent veins and minor hypotrophy/hypertrophy that differs from Klippel–Trenaunay syndrome (capillary‐lymphatic‐venous malformation) but belongs at the minor end of the spectrum of vascular disorders with overgrowth.     

Management of digital mucous cysts: a systematic review and treatment algorithm

Digital mucous cysts (DMC) are benign, highly recurrent lesions of the digits. To date, there is still no treatment agreement on the treatment of DMC. Herein, we review available data on treatment modalities, including both surgical and nonsurgical techniques, and to provide a practical algorithm for the management of DMC. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane databases. Articles studying the management of DMC were included in this review. A total of 40 articles were included in the review. The five most frequently used treatments for DMC were surgery (n = 849), expression of cyst content (n = 132), sclerotherapy (n = 119), corticosteroid injection (n = 108), and cryotherapy (n = 103). Surgery yielded the highest cure rate among all treatment modalities (95%) compared to sclerotherapy (77%), cryotherapy (72%), corticosteroid injection (61%), and expression of cyst content (39%) (P < 0.001). Surgery should be considered as the first‐line treatment for DMC. Second‐line treatments include sclerotherapy and cryotherapy. Third‐line treatments include corticosteroid injections, expression of cyst content, and less‐studied modalities. Surgery showed the highest cure rates. Future adequately designed randomized controlled trials are warranted to compare different treatment modalities.     

Rebounding triad (severe itching,dryness and burning) after facial corticosteroid discontinuation defines a specific class of corticosteroid‐dependent dermatitis

In patients with dermatitis, the sudden discontinuation of topical corticosteroid (TC) use after long‐term treatment could cause flaring symptoms (named “rebounding responses”). Diagnostic criteria for facial corticosteroid‐dependent dermatitis (FCDD) are vague and uncertain. We aim to define a category of patients with clinical rebounding triad including severe itching, dryness and burning. Patients with FCDD (n = 268) were evaluated to determine distinctive rebounding triad manifestations after TC cessation. Data on history of facial TC use and rebounding presentations were collected. A group of chronic dermatitis patients (n = 83) with rebounding triad after TC discontinuation were enrolled and added to patients with FCDD presenting triad symptoms. Patients without triad were compared with triad‐positive patients. Eighty‐five patients who displayed triad manifestations after TC cessation showed longer (93.1 ± 53.6 vs 9.6 ± 5.5 weeks, P < 0.001) and more frequent (7.7 ± 4.5 vs 2.3 ± 1.6 times/week, P < 0.001) use of TC. Similar results were observed after adding 83 dermatitis patients who experienced triad after TC cessation. Multivariate analysis showed that mean duration of TC use (odds ratio [OR] = 1.83, 95% confidence interval (95% CI) = 1.042–3.218, P = 0.035) and mean frequency of TC use (OR = 2.802, 95% CI = 1.135–6.918, P = 0.025) were independent predictors of rebounding triad after TC cessation. Duration and frequency of TC use were the main factors predicting rebounding triad.     

Drug survival rates in patients with psoriasis after treatment with biologics

Clinically, patients' adherence to biologic treatment is not only related to efficacy but also to adverse events, cost and other factors. To evaluate long‐term viability of biologic treatment, both the percentage of and reasons for discontinuation of treatment were investigated. In this study, patients treated with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were included and observed for 12 months. Clinical efficacy was evaluated using a 75% reduction of Psoriasis Area and Severity Index score (PASI‐75), and patients who discontinued treatment were considered as not having achieved PASI‐75. In addition, drug survival rate (DSR) was investigated. In patients treated with infliximab, PASI‐75 was 68.4% and DSR was 73.3% by the end of treatment. In patients treated with adalimumab, PASI‐75 was 50.8% and DSR was 79.7%. In patients treated with ustekinumab, PASI‐75 was 63.3% and DSR was 96.7%. Several patients discontinued treatment because of insufficient efficacy due to secondary failure in infliximab or primary failure in adalimumab. To increase treatment efficacy, it will be necessary for these patients to use an additional concomitant treatment. Higher efficacy is expected with biologics than with conventional treatments; however, the actual clinical efficacy over a long period of time may be insufficient if they are used without any concomitant treatments.     

The role of phototherapy in the surgical treatment of vitiligo: a systematic review

Vitiligo is frequently treated with the combination of phototherapy and melanocyte transplantation. However, the additional benefit of phototherapy is unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The objective of this systematic review was to identify whether phototherapy improves the outcome of melanocyte transplantation in vitiligo. We searched and screened for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included all clinical studies investigating melanocyte transplantation combined with phototherapy. After screening and selection of abstracts and full‐texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n = 19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy.     

Scleromyxedema and lichen myxedematosus: Is it associated with viral hepatitis?

Scleromyxedema (SM) was previously known to be associated with monoclonal gammopathy. The association of SM and its counterpart lichen myxedematosus (LM) with chronic hepatitis has rarely been reported. We retrospectively reviewed medical records and histopathological reports of consecutive patients who presented at our department with the diagnosis of SM or LM from January 2001 to September 2017. The patients’ demographic details, cutaneous presentation, associated underlying diseases and hepatitic profile were studied and compared with previous published cases. In all, 28 patients were enrolled, including one SM, 19 LM and eight atypical LM. Of the patients, 50% (n = 14/28) had hepatitis. Of these, 21.4% (n = 6/28) had hepatitis C, 10.7% (n = 3/28) hepatitis B, 7.1% (n = 2/28) concurrent hepatitis B and C, whereas 10.7% (n = 3/28) had alcoholic liver disease. The prevalence of hepatitis C in our patients was 6.5‐times higher than that of the general population (28.6% vs 4.4%) and the prevalence of hepatitis B was similar (17.9% vs 17.3%). Polyclonal gammopathy was found in 28.6% (n = 8/28) of the patients and monoclonal gammopathy was found in 7.1% (n = 2/28). The extent of clonality did not correlate with disease severity. Our study did not notice a significant association with monoclonal gammopathy but the prevalence of hepatitis C was found to increase 6.5‐times in these patients compared with the general population. We recommend dermatologists to be aware of hepatitis investigations in such patients and future studies are warranted to understand the mechanism behind such association.     

Trends in the prognosis of metastatic melanoma in the era of targeted therapy and immunotherapy: A single‐institution survey in Japan

Advances in anticancer therapy, including the development of targeted therapy and immunotherapy, have drastically changed treatment options for metastatic melanoma. However, to date, only a few studies have been published that directly compare overall survival (OS) before and after introduction of these new therapeutic options in Japan. We retrospectively surveyed patients with metastatic melanoma treated in our hospital between 1989 and 2019 to investigate the OS benefit of the new therapies. A total of 115 patients with metastatic melanoma (cutaneous origin, 92; mucosal, 14; uveal, two) were included in the study. Kaplan–Meier analysis showed that the patient group receiving targeted therapy/immunotherapy (TT/IT) (n = 47) had a median OS of 19.0 months, which was longer than that in patients receiving conventional chemotherapy (n = 42, 8.0 months) or no treatment (n = 26, 6.0 months) (P < 0.001). In the subgroup analysis performed for the TT/IT group, patients of younger age and with the BRAF mutation had significantly improved OS. As the number of treatment lines increased, the median OS tended to become longer. Our real‐world data confirmed an improvement of median OS upon the introduction of the new therapies for metastatic melanoma. However, the long‐term OS benefit was limited, possibly because of racial differences in some of the clinical characteristics. To improve the overall melanoma prognosis, the entire treatment strategy, including perioperative therapy needs strengthening.     

TNF α‐induced leukocyte–endothelial cell interactions show marked interindividual differences independent of the clinical response to adalimumab

The responses of patients with psoriasis to TNFα‐antagonists show interindividual differences. Here, TNFα‐incubation induced endothelial adhesion molecules, a prerequisite for leucocyte recruitment to inflamed tissues. Using a standardized flow chamber system equipped with near‐confluent endothelial cells and a mobile phase containing human leucocytes, proportions of leucocytes interacting with endothelial cells were remarkably different between individual donors (up to 3.5‐fold), regardless of whether the leucocytes originated from patients with psoriasis (n = 10) or healthy donors (n = 10). Adalimumab abrogated adhesion molecule induction and interactions with leucocytes when present prior to or simultaneously with, but not after exposure of the cultures to TNFα. This pattern was seen similarly with leucocytes from healthy donors (n = 4), and patients whose psoriasis responded well to adalimumab (n = 5) and non‐responders (n = 5). Thus, although considerable interindividual differences of leucocyte–endothelial cell interactions were demonstrated ex vivo in a TNFα‐governed microenvironment, such differences are not associated with individual responses to treatment with adalimumab in vivo.     

Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAFV600 mutations

We investigated the efficacy and safety of vemurafenib in Japanese patients with unresectable or recurrent melanoma with BRAF^V600 mutations. This was a two‐step open‐label multicenter phase I/II study. Step 1 evaluated the initial safety of vemurafenib 960 mg administrated p.o. twice daily in three patients. In step 2, eight patients received vemurafenib 960 mg administrated p.o. twice daily for 28‐day treatment cycles; the primary outcome measure was response rate, as determined by independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AE) experienced by five or more patients were arthralgia (n = 10), myalgia (n = 8), alopecia (n = 7), and rash, maculopapular rash and decreased appetite (n = 5 each). Three patients had grade 3 AE. One serious AE occurred in one patient (abnormal hepatic function). Six patients required dose reduction because of AE. One patient died within 28 days after the last dose, but death was caused by disease progression and not associated with the study drug. In the eight patients in step 2, overall response rate was 75.0%, none had a complete response and six had a partial response (75.0%). Median response duration was 240.0 days, disease control rate 87.5%, median progression‐free survival 416.0 days and median overall survival 443.0 days. In conclusion, vemurafenib treatment resulted in an overall response rate of 75% in Japanese patients with metastatic melanoma with BRAF^V600 mutations. All toxicities were manageable.     

Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by mutation in the NF1 tumor‐suppressor gene, and may sometimes manifest in a mosaic form. “Segmental NF1” is generally assumed to be the result of somatic mosaicism for a NF1 mutation, and patients with mosaic NF1 have typical features of NF1 limited to specific body segments. The clinical features of 58 patients (42 females and 16 males; aged 1–69 years; mean age, 23.4 years) with mosaic NF1 seen at the Jikei University Hospital during 2004–2007 and at the Jikei University Daisan Hospital during 2007–2011, were retrospectively studied. Somatic or gonosomal mosaicism was not investigated. Patients were classified into four groups: (i) pigmentary changes (café‐au‐lait spots and freckling) only (n = 32); (ii) neurofibromas only (n = 5); (iii) neurofibromas and pigmentary changes (n = 13); and (iv) solitary plexiform neurofibromas (n = 8). The area of involvement was variable. The majority of patients were asymptomatic, except patients with plexiform neurofibromas who presented most commonly with pain or tenderness. Lisch nodules were rarely seen. Only four of our 58 patients (6.9%) had specific NF1 complications, including language delay (n = 1) and bone deformity (n = 3). Two patients were ascertained through their children with generalized NF1. Patients with mosaic NF1 are at low risk of developing disease‐associated complications, except patients with plexiform neurofibromas. However, they need to be aware of the small risk of having a child with generalized NF1.     

Optical coherence tomography for presurgical margin assessment of non‐melanoma skin cancer – a practical approach

In the clinical setting, optical coherence tomography (OCT) is applicable for the non‐invasive diagnosis of skin cancer and may in particular be used for margin definition prior to excision. In this regard, OCT may improve the success rate of removing tumor lesions more effectively, preventing repetitive excision, which may subsequently result in smaller excisions. In this study, we have aimed to evaluate the applicability of OCT for in vivo presurgical margin assessment of non‐melanocytic skin tumors (NMSC) and to describe the feasibility of different scanning techniques. A total number of 18 patients planned for excision of lesions suspicious of NMSC were included in this study. Based on OCT, we defined the specific tumor margins on 19 lesions preoperatively using different scanning modalities. Sixty‐one margin points and five complete tumor margins were analysed on 18 patients with a total of 19 lesions including 63% basal cell carcinoma (BCC) (n = 12), 16% (n = 3) squamous cell carcinoma (SCC) and 21% of other types of skin tumors (n = 4) were classified. In 84% of the cases (n = 16), the OCT‐defined lateral margins correctly indicated complete removal of the tumor. The surgical margins chosen by the surgeon never fell below the OCT‐defined margin. Regarding the techniques of marginal definition, punctual tumor border scan in the perpendicular direction, with an extension of free‐run scans for unsure cases can hardly be recommended. This study shows that suspected NMSC can effectively be confirmed, and furthermore, resection margin can be minimized under OCT control without reducing the rate of complete removal.     

Early Versus Later Presentations of Venous Malformations: Where and Why?

Venous malformations (VMs) are congenital anomalies of the venous vasculature, but not all are evident at birth. The factors that lead to presentation later in life are not well understood. The objective of this retrospective cohort study of patients with VMs evaluated at the University of California at San Francisco Birthmarks and Vascular Anomalies Center from 2005 to 2009 was to investigate the clinical presentation of VMs and correlate these features with different types of tissues (e.g., skin, subcutis, intramuscular). Main outcomes included the age at which lesions were first noticed, tissue type involved, presenting signs and symptoms, aggravating factors, and morbidities. A total of 115 subjects was included. The mean age when VM was first noted was 6.7 ± 0.9 years. Tissue types involved included skin/subcutaneous (46%); intramuscular (40%); and bone, tendon, or joint (14%). Presenting signs/symptoms included soft tissue swelling (44%), discrete mass (34%), pain (33%), and skin discoloration (26%). When compared with VMs limited to the skin or subcutis, those restricted to the intramuscular compartment were less likely to present at birth (27% vs 53%, p < 0.05) but were more frequently painful (79% vs 60%, p < 0.05) and contained more phleboliths (28% vs 11%, p < 0.05), and were associated with more exercise limitation (35% vs 16%, p < 0.05). VMs differ in age of onset, clinical features, and complications based on differing tissues and sites of involvement, with isolated intramuscular involvement associated with later presentation and greater morbidity.     

Retrospective analysis of 12 Korean patients with paraneoplastic pemphigus

Paraneoplastic pemphigus (PNP) is a rare, life‐threatening, autoimmune, mucocutaneous blistering disease associated with neoplasia. Both humoral and cellular immunity are involved in the pathogenesis of PNP. Characteristically, PNP has a diverse spectrum of clinical and immunopathological features. We retrospectively analyzed 12 Korean patients with PNP who were diagnosed between 1993 and 2011. We performed analysis of the clinical features, clinical outcomes, underlying neoplasia, histological features and laboratory findings. All of the patients except one had severe mucosal involvement. Two patients had only mucosal lesions but no cutaneous involvement was observed. Erythema multiforme or lichen planus‐like eruptions rather than bullous lesions were more commonly observed skin rashes. The most common histological features were interface dermatitis and apoptotic keratinocytes. There were associated hematological‐related neoplasms in 11 patients, with Castleman's disease (n = 4) as the most frequent. Twelve patients were followed for 5–148 months (mean, 43.0). The prognosis depended on the nature of the underlying neoplasm. Six patients died due to respiratory failure (n = 3), postoperative septicemia (n = 1), lymphoma (n = 1) and sarcomatosis (n = 1). The 2‐year survival rate was 50.0%, and the median survival period after diagnosis was 21.0 months. Immunoblotting was performed in 12 patients and autoantibodies to plakins were detected in 11 patients. The results of this study demonstrated the clinical, histological and immunological diversity of PNP. Widely accepted diagnostic criteria that account for the diversity of PNP are needed.     

Long‐Term Treatment with Oral Propranolol Reduces Relapses of Infantile Hemangiomas

Oral propranolol (OP) has been shown to be effective in the treatment of complicated infantile hemangiomas (IHs), but optimal treatment duration to avoid relapses after stopping OP treatment has not been established. The objective of this study was to compare the frequency of relapses in long‐term OP treatment with that of short‐term OP treatment. This was a retrospective cohort study of 30 patients with complicated IHs who received treatment with OP. Patients were divided into two groups: OP treatment of 8 months or less and OP treatment of longer than 8 months. OP was started at 1 mg/kg/day in three doses every 8 hours for 1 week and increased to 1.5 to 4 mg/kg/day afterward. Ultrasound was used to objectively measure the response to treatment. Clinical and ultrasound assessment showed a decrease in IH size and resolution of complications in all patients (n = 30). In the short‐term group (n = 10), nine patients (90%) relapsed after stopping treatment. In the long‐term group (n = 20), the duration of treatment was 12 months in all patients, and only 1 patient out of the 20 treated (5%) showed relapse 2 months after finishing the full treatment (odds ratio = 18, 95% confidence interval 2.6, 123, p < 0.001. Twelve months of treatment of IH with OP is associated with a significantly lower rate of relapse than with shorter treatment.     

Effects of non‐amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma

Subungual melanomas (SUM) are rare, and amputation is often required. Non‐amputative wide local excision (WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5‐mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive group) and 12 patients with more than 0.5‐mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow‐up period (24–207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re‐excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long‐term follow up is required to evaluate adequately the risks associated with a non‐amputative WLE for in situ and invasive SUM.     

Non‐invasive subcutaneous fat reduction: a review

The risks, financial costs and lengthy downtime associated with surgical procedures for fat reduction have led to the development of a number of non‐invasive techniques. Non‐invasive body contouring now represents the fastest growing area of aesthetic medicine. There are currently four leading non‐invasive techniques for reducing localized subcutaneous adipose tissue: low‐level laser therapy (LLLT), cryolipolysis, radio frequency (RF) and high‐intensity focused ultrasound (HIFU). To review and compare leading techniques and clinical outcomes of non‐invasive subcutaneous fat reduction. The terms ‘non‐invasive’, ‘low‐level laser’, ‘cryolipolysis’, ‘ultrasound’ and ‘radio frequency’ were combined with ‘lipolysis’, ‘fat reduction’ or ‘body contour’ during separate searches in the PubMed database. We identified 31 studies (27 prospective clinical studies and four retrospective chart reviews) with a total of 2937 patients that had been treated with LLLT (n = 1114), cryolipolysis (n = 706), HIFU (n = 843) or RF (n = 116) or other techniques (n = 158) for fat reduction or body contouring. A majority of these patients experienced significant and satisfying results without any serious adverse effects. The studies investigating these devices have all varied in treatment regimen, body locations, follow‐up times or outcome operationalization. Each technique differs in offered advantages and severity of adverse effects. However, multiple non‐invasive devices are safe and effective for circumferential reduction in local fat tissue by 2 cm or more across the abdomen, hips and thighs. Results are consistent and reproducible for each device and none are associated with any serious or permanent adverse effects.     

Balance of Treg versus T‐effector cells during systemic treatment with adalimumab and topical treatment with calcipotriol–betamethasone dipropionate ointment

Diminished suppressive capacity of regulatory T cells (Treg) has been demonstrated in blood and in lesional skin of psoriatic patients. Treatment with anti‐TNFα restored the number and function of circulating Treg in psoriasis. We aimed to study Treg in the skin of psoriatic patients undergoing topical treatment with calcipotriol–betamethasone dipropionate (CBD) ointment (n = 12) or systemic treatment with anti‐TNFα agent adalimumab (n = 10). Skin biopsies were collected from patients with chronic plaque psoriasis who responded to the above‐mentioned treatments with a SUM‐score improvement of at least 50% (at the end of treatment). Biopsies were processed for immunohistochemistry. As Treg function is associated with a numerical balance between Treg and effector T cells, Foxp3/CD4 ratios were calculated. It appeared that both treatments cause a significant decrease in the presence of Foxp3+ cells. However, in patients that were treated with CBD ointment, we observed lower Foxp3/CD4 ratios after 8 weeks of treatment compared to baseline (t = 0: 0.41 ± 0.08; t = 8: 0.22 ± 0.04, P = 0.033), whereas in patients who were treated with adalimumab we observed an increase of the Foxp3/CD4 ratios after 1.5 and 16 weeks of treatment compared to baseline (t = 0: 0.25 ± 0.04; t = 1.5: 0.32 ± 0.06; t = 16: 0.49 ± 0.10, P = 0.15). Based on Foxp3/CD4 ratios, we can conclude that adalimumab treated skin differs from CBD treated skin with regard to the anti‐inflammatory/inflammatory balance. We suggest that, in contrast to CBD ointment, adalimumab favours local Treg function in the skin.