COVID-associated complications after reconstructive breast surgery: a retrospective cohort study.

PURPOSE: The COVID pandemic significantly influenced reconstructive breast surgery regimens. Many surgeries were cancelled or postponed. COVID entails not only respiratory, but also coagulative symptoms. It, therefore, potentially increases the risk of postoperative complications. The incidence of perioperative COVID infection and its influence on postoperative recovery after reconstructive breast surgery is still unknown. METHODS: This dual center retrospective cohort study included patients that underwent reconstructive breast surgery between March 2020 and July 2021. Post-mastectomy autologous or implant-based breast reconstruction (ABR; IBR), as well as post-lumpectomy oncoplastic partial breast reconstruction (PBR) were eligible. Patient data were extracted from electronic medical records. Data regarding COVID-19 infection was collected through a questionnaire. The primary outcome was complication rate. RESULTS: The ABR, IBR and PBR groups consisted of 113 (12 COVID-positive), 41 (2 COVID-positive) and 113 (10 COVID-positive) patients. In the ABR and PBR groups, postoperative complications occurred significantly more often in patients with perioperative COVID-infection. Especially impaired wound healing occurred significantly more often in the ABR and PBR breasts, but also at the donor site of ABR patients with perioperative COVID. CONCLUSION: Perioperative COVID-infection increases susceptibility to complicated wound healing after reconstructive breast surgery. A possible explanation lies in the dysregulation of haemostasis by the virus, and its direct effects on microvasculature. A hypercoagulable state results. We recommend to postpone elective breast surgery for 4-6 weeks after COVID-19 infection. Also, precautionary measures remain important to minimize the risk of perioperative COVID-19 infection.

The impact of using the internal mammary artery as a recipient vessel on medial mastectomy skin flap perfusion in autologous breast reconstruction: An observational study using indocyanine green.

BACKGROUND: The internal mammary artery (IMA) is the preferred recipient vessel for microvascular anastomosis in immediate autologous breast reconstruction following skin-sparing mastectomy (SSM). Although the IMA accounts for approximately 60% of the blood supply to the breast, the exact contribution to the mastectomy skin flap perfusion is unclear. The aim of this observational study was to investigate the impact of using the IMA as a recipient vessel on medial mastectomy skin flap perfusion assessed with indocyanine green angiography (ICGA). METHODS: This observational study included ten consecutive women who underwent immediate autologous breast reconstructions following SSM. Two intraoperative indocyanine green (ICG) assessments were performed to assess tissue perfusion of the upper and lower part of the medial mastectomy skin flap: the first following the SSM and the second after clamping the IMA. During a 120-second angiography, three additional images were made after 60, 90, and 120 s. The ICG inflow time and mean, minimum, and maximum fluorescence intensities (FIs) were obtained. RESULTS: Four unilateral and six bilateral autologous breast reconstructions were included. There was no difference in tissue perfusion when comparing the inflow time (24.1 s vs. 23.0 s, P = 0.348), the mean FI (131.4 vs. 124.0, P = 0.126), minimum FI (28.6 vs. 33.4, P = 0.086), and maximum FI (253.1 vs. 247.6, P = 0.166) before and after clamping the IMA. CONCLUSION: According to this study, the use of the IMA as a recipient vessel does not reduce medial mastectomy skin flap perfusion in patients undergoing immediate autologous breast reconstructions following SSM.

The influence of neoadjuvant chemotherapy on complications of immediate DIEP flap breast reconstructions.

PURPOSE: The impact of neoadjuvant chemotherapy on the surgical outcomes of immediate breast reconstruction remains controversial. The aim of this study was to analyze the incidence of complications of immediate deep inferior epigastric artery perforator (DIEP) flap breast reconstructions in patients who received neoadjuvant chemotherapy compared to patients without neoadjuvant chemotherapy prior to surgery. METHODS: A multicenter, retrospective cohort study was conducted of all patients who underwent immediate DIEP flap breast reconstruction between January 2010 and June 2017. Patients were divided in two groups as breast reconstructions with or without neoadjuvant chemotherapy, respectively. The primary outcome was the incidence of postoperative flap re-explorations, recipient-site complications and donor-site complications. RESULTS: In total 432 immediate DIEP flap breast reconstructions in 326 patients were included. Forty-eight patients (n = 67 flaps) received neoadjuvant chemotherapy prior to immediate breast reconstruction and 278 patients (n = 365 flaps) did not. No statistically significant differences for any major (4.5% vs. 10.4%; p = 0.175) or minor (16.4% vs. 24.7%; p = 0.191) recipient-site complication were observed. Donor-site complications were recorded in 9 (18.8%) and 62 (22.2%) patients, respectively (p = 0.587). There was no difference in need for flap re-exploration between groups (3.0% vs. 8.5%; p = 0.139). Correction for potential confounding variables did not result in significant differences. CONCLUSIONS: This study demonstrated similar complication rates for patients with and without neoadjuvant chemotherapy prior to immediate breast reconstruction, indicating that it is safe to perform an immediate DIEP flap breast reconstruction after neoadjuvant chemotherapy.

Short-term cost-effectiveness of one-stage implant-based breast reconstruction with an acellular dermal matrix versus two-stage expander-implant reconstruction from a multicentre randomized clinical trial.

BACKGROUND: Implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure and its economic impact is significant. This study aimed to analyse whether a direct one-stage IBBR with use of an acellular dermal matrix (ADM) is more cost-effective than two-stage (expander-implant) breast reconstruction. METHODS: The BRIOS (Breast Reconstruction In One Stage) study was an open-label multicentre RCT in which women scheduled for skin-sparing mastectomy and immediate IBBR were randomized between one-stage IBBR with ADM or two-stage IBBR. Duration of surgery and hospital stay, and visits for the primary surgery, unplanned and cosmetic procedures were recorded. Costs were estimated at an institutional level. Health status was assessed by means of the EuroQol Five Dimensions 5L questionnaire. RESULTS: Fifty-nine patients (91 breasts) underwent one-stage IBBR with ADM and 62 patients (92 breasts) two-stage IBBR. The mean(s.d.) duration of surgery in the one-stage group was significantly longer than that for two-stage IBBR for unilateral (2·52(0·55) versus 2·02(0·35) h; P < 0·001) and bilateral (4·03(1·00) versus 3·25(0·58) h; P = 0·017) reconstructions. Costs were higher for one-stage compared with two-stage IBBR for both unilateral (€12 448 (95 per cent c.i. 10 722 to 14 387) versus €9871 (9373 to 10 445) respectively; P = 0·025) and bilateral (€16 939 (14 887 to 19 360) versus €13 383 (12 414 to 14 669); P = 0·002) reconstructions. This was partly related to the use of relatively expensive ADM. There was no difference in postoperative health status between the groups. CONCLUSION: One-stage IBBR with ADM was associated with higher costs, but similar health status, compared with conventional two-stage IBBR. Registration number: NTR5446 ( http://www.trialregister.nl).

Breast sensibility after mastectomy and implant-based breast reconstruction.

PURPOSE: The aim of the study is to evaluate the level of sensible impairment after mastectomy or implant-based breast reconstruction (IBBR). In addition, factors influencing breast sensibility were evaluated. METHODS: A cross-sectional study was performed in Maastricht University Medical Center between July 2016 and August 2018. Women with unilateral mastectomy with or without IBBR were included. Objective sensory measurements were performed using Semmes-Weinstein monofilaments. Their healthy breast served as control, using a paired t test. Differences between mastectomy with and without IBBR were evaluated using the independent t test. Linear regression was performed to evaluate the association between patient characteristics on breast sensibility. The paired t test was used to evaluate in which part of the breast the sensibility is best preserved. RESULTS: Fifty-one patients were eligible for inclusion. Sixteen patients underwent IBBR after mastectomy. Twenty-three patients received radiotherapy and 35 patients received chemotherapy. Monofilament values were significantly higher in the operated group compared to the reference group (p < 0.001). Linear regression showed a statistically significant association between IBBR and objectively measured impaired sensation (p = 0.008). After mastectomy, the cutaneous protective sensation is only diminished. After IBBR, it is lost in the majority of the breast. The medial part of the breast was significantly more sensitive than the lateral part in all operated breasts (p < 0.001). CONCLUSION: IBBR has a significantly negative impact on the breast sensibility compared to mastectomy alone. This study shows that the protective sensation of the skin in the breast is lost after IBBR. To our knowledge, this is the first study to evaluate the level of sensible impairment after mastectomy or IBBR. More research is necessary to confirm these results.

Predictors of complications after direct-to-implant breast reconstruction with an acellular dermal matrix from a multicentre randomized clinical trial.

BACKGROUND: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct-to-implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two-stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM-assisted breast reconstruction. METHODS: Data were obtained from the BRIOS study, including all patients treated with DTI ADM-assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. RESULTS: Fifty-nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. CONCLUSION: Breast size appeared to be the most significant predictor of complications in DTI ADM-assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl).

A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study.

BACKGROUND: Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars. METHODS: Fifty-eight patients with hypertrophic scars (n = 31) and keloid scars (n = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly (P < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3-4 months, 4-6 months, and >12 months after start of therapy in both keloids and hypertrophic scars. CONCLUSIONS: This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.Level of evidence: Level IV, therapeutic study.

Complications following immediate compared to delayed deep inferior epigastric artery perforator flap breast reconstructions.

PURPOSE: As more breast cancer patients opt for immediate breast reconstruction, the incidence of complications should be evaluated. The aim of this study was to analyze the recipient-site complications and flap re-explorations of immediate compared to delayed deep inferior epigastric artery perforator (DIEP) flap breast reconstructions. METHODS: For this multicenter retrospective cohort study, the medical records of all patients who underwent DIEP flap breast reconstruction in three hospitals in the Netherlands between January 2010 and June 2017 were reviewed. Patient demographics, risk factors, timing of reconstruction, recipient-site complications, and flap re-explorations were recorded. RESULTS: A total of 910 DIEP flap breast reconstructions (n = 397 immediate and n = 513 delayed reconstructions) in 737 patients were included. There were no significant differences in major complications or flap re-explorations between immediate and delayed reconstructions. The total flap failure rate was 1.5 and 2.5% in the immediate and delayed group, respectively. Significantly more hematomas (OR 2.91; 95% CI 1.59-5.30; p = 0.001) and seromas (OR 3.60; 95% CI 1.14-11.4; p = 0.029) occurred in immediate reconstructions, whereas wound problems were more frequently observed in delayed reconstructions (OR 1.99; 95% CI 1.27-3.11; p = 0.003). Correction for potential confounders still showed significant differences for hematoma and seroma, but no longer for wound problems (p = 0.052). CONCLUSIONS: This study demonstrated similar incidences of major recipient-site complications and flap re-explorations between immediate and delayed DIEP flap breast reconstructions. However, hematoma and seroma occurred significantly more often in immediate reconstructions, while wound problems were more frequently observed in delayed reconstructions.

Sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions: A systematic review.

BACKGROUND: The sensory recovery of the reconstructed breast is an undervalued topic in the field of autologous breast reconstruction. This systematic review aimed to evaluate the available literature on the sensory recovery of the breast after innervated and non-innervated autologous breast reconstructions and to assess the possible benefits of sensory nerve coaptation compared to spontaneous reinnervation of the flap. METHODS: A comprehensive literature search was conducted in PubMed, Embase and the Cochrane Library to identify all eligible studies regarding the sensory recovery of all types of innervated and non-innervated autologous breast reconstructions. RESULTS: The search yielded 334 hits, of which 32 studies concerning 1177 breast reconstructions were included. The amount of heterogeneity between the studies was high, which made the pooling of data difficult. The studies indicated that spontaneous reinnervation of autologous breast reconstructions occurred to a variable extent, depending on how and when it was measured. Despite these variable results, the sensory recovery of innervated flaps, however, was superior, started earlier and gradually improved over time with a higher chance of approaching normal values than non-innervated flaps. There is a lack of studies that assess the return of erogenous sensation and quality of life. CONCLUSION: The current evidence shows that nerve coaptation results in superior sensory recovery of the reconstructed breast compared to spontaneous reinnervation of the flap. This review illustrates that more standardised, high-quality studies with adequate sample sizes are needed to objectively evaluate the sensory recovery of the breast after autologous breast reconstructions.

Complications in unilateral versus bilateral deep inferior epigastric artery perforator flap breast reconstructions: A multicentre study.

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is the first choice for autologous breast reconstruction. The aim of this retrospective cohort study was to analyse the recipient- and donor-site complications and compare them between unilateral and bilateral DIEP flap breast reconstructions. METHODS: Between January 2010 and December 2014, 530 DIEP flap reconstructions were performed in 426 consecutive patients in three Dutch hospitals. Major and minor complications were categorised into recipient- and donor-site complications. Post-operative flap re-explorations were recorded. RESULTS: Of the total 530 DIEP flap reconstructions performed (322 unilateral, 104 bilateral), recipient-site complications were major in 9.8% and minor in 20.2%. The patients developed fat necrosis (unilateral 14.0% vs. bilateral 7.7%; OR 1.950; 95% CI 1.071-3.550; p = 0.027) and infection (unilateral 5.6% vs. bilateral 1.9%; OR 3.020; 95% CI 1.007-9.052; p = 0.039) at the recipient site significantly more frequently in the unilateral DIEP flap reconstructions. The donor-site complications were major in 0.9% and minor in 19.5% of the cases. Body mass index (BMI) was significantly associated with complications (donor site: OR 1.137; 95% CI 1.075-1.201; p < 0.001, recipient site: OR 1.073; 95% CI 1.009-1.142; p = 0.026). Flap re-explorations were performed in 5.7% (n = 30) of the cases. Total flap loss occurred in 3.0% (n = 16) of the cases. CONCLUSIONS: Bilateral DIEP flap breast reconstructions can be performed with the same percentage of complications and re-explorations as unilateral reconstructions and even result in less fat necrosis and infection at the recipient site. Higher BMIs are significantly associated with recipient- and donor-site complications.

Single-stage breast reconstruction using Strattice™: A retrospective study.

INTRODUCTION: Strattice™, a porcine acellular dermal matrix, has emerged as a product to augment implant-based breast reconstruction. It aims to resolve problems related to poor tissue coverage of the implant. Presently, evidence justifying the use of Strattice in breast reconstruction is lacking. The objective of this study is to assess the clinical outcomes of a patient cohort that underwent single-stage implant-based breast reconstruction with the additional use of Strattice. METHODS: We conducted a retrospective chart review of patients who underwent single-stage breast reconstruction with the use of Strattice. All cases of breast reconstruction after oncologic or prophylactic mastectomy between 2010 and 2014 in one of eight different centres in the Netherlands were included. Patient demographics, treatment characteristics and clinical outcome data were collected. The outcomes were presented using descriptive statistics, and the associations were evaluated using Fisher's exact test. RESULTS: Eighty-eight patients who underwent either unilateral (60 patients) or bilateral (25 patients) (n = 110 breasts) single-stage breast reconstruction with the use of Strattice were identified. The indication for mastectomy was therapeutic in 69.1% (76) of cases and prophylactic in 30.9% (34) of cases. The reported minor complications included seroma (20.9%), skin necrosis (20.0%), wound dehiscence (11.8%), erythema/inflammation (14.5%) and infection (11.8%). In 22 breasts (22.7%), reoperation was necessary, with explantation of the implant in 11 breasts (11.8%). CONCLUSIONS: In this cohort, the total complication rate was very high (78%). Although most complications were minor, reoperation was performed in 22.7%, with explantation of the implant in 11.8% of breasts. We suggest that patient selection, experience of the surgeon and handling of early complications are factors playing a crucial role in the success of the operation. The use of a Strattice sheet in single-stage implant-based breast reconstruction may be a promising technique, but more evidence from prospective, randomized studies is necessary to justify its use. LEVEL OF EVIDENCE: IV.

Septocutaneous tensor fasciae latae perforator flap for breast reconstruction: radiological considerations and clinical cases.

INTRODUCTION: The deep inferior epigastric artery perforator (DIEP) flap is the first choice in autologous breast reconstruction; in cases when it cannot be used, alternative flaps are available. A radiological study and clinical cases using septocutaneous tensor fasciae latae (sc-TFL) flap for breast reconstruction are presented. MATERIALS: Magnetic resonance angiographies (MRAs) of 55 patients were evaluated. The pedicle and the perforators of the TFL were studied. Five consecutive sc-TFL flaps for breast reconstruction were performed. RESULTS: Thirty-seven MRA scans were included. There was a mean of 1.5 septocutaneous perforators per thigh. The mean pedicle length was 8.3 cm. Every perforator originated from a branch of the lateral circumflex femoral artery (LCFA). The LCFA originated from the arteria femoralis profunda in 89.2% of cases. In the vertical plane, the mean distance of the perforator from the antero-superior iliac spine was 8.7 cm. There were no major complications in the five sc-TFL performed. CONCLUSION: On MRA, the septocutaneous pedicle of the TFL perforator flap was consistently present. MR angiographic assessment of the septocutaneous branches was very helpful in the preoperative evaluation of our patients. Dissection of the sc-TFL can be performed in a supine position simultaneously with mastectomy and/or dissection of the mammary vessels. Finally, the donor-site scar can be hidden by underwear, giving minimal deformity. We recommend the sc-TFL flap as a good alternative to the DIEP flap for autologous breast reconstruction. Preoperative imaging is mandatory for correct planning of the flap.

No increase of local recurrence rate in breast cancer patients treated with skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The aim of this study was to evaluate the incidence of local recurrence after SSM with IBR and to determine whether complications lead to postponement of adjuvant therapy. METHOD: Patients that underwent IBR after SSM between 2004 and 2011 were included. RESULTS: A total of 157 reconstruction procedures were performed in 147 patients for invasive breast cancer (n = 117) and ductal carcinoma in situ (n = 40). The median follow-up was 39 months [range 6-97]. Estimated 5-year local recurrence rate was 2.9% (95% CI 0.1-5.7). The median time to start adjuvant therapy was 27.5 days [range 19-92] in 18 patients with complications, and 23.5 days [range 8-54] in 46 patients without complications (p = 0.025). CONCLUSION: In our single-institution cohort, IBR after SSM carried an acceptable local recurrence rate. Complications caused a delay of adjuvant treatment but this was within guidelines and therefore not clinically relevant.

Smoking and its effect on scar healing.

Scar formation is influenced by several factors such as wound infection, tension, wound depth and anatomical localization. Hypertrophic scarring is often the result of an imbalance in the wound and scar healing process. The exact underlying pathophysiological mechanism remains unclear. Smoking has a higher risk of postoperative complications probably due to a diminished macrophage induction. Following our clinical impression that smokers without postoperative wound infections show esthetically better scars, we evaluated the scars after a reduction mammaplasty in smoking and nonsmoking patients in a prospective clinical trial. Between July 2006 and September 2007, 13 smokers and 30 non smokers with a reduction mammaplasty were included. They were recruited from Viecuri Medical Centre and Atrium Medical Centre in the Netherlands after written consent. Surgical data and data of the patients' condition were collected. Follow-up for erythema values of the scars was done with a colorimeter (The Minolta CR-300, Minolta Camera Co., Ltd., Osaka Japan) at 1, 3, 6 and 9 months postoperatively on four standardized postsurgical sites. ANOVA and Chi-square test were used for statistical analysis. In the smoking group, the scars were significantly less red compared to the nonsmoking group. No significant differences were found in BMI, resection weight and drain production between both groups. Although smoking is certainly not recommended as a preventive therapy to influence scar healing, this study confirms our assumption that smokers tend to have faster and less erythemateous scar healing to nonsmokers. Further research is needed to understand the mechanism of the effect of smoking on scars.

Neurovenous superficial inferior epigastric flaps in rats.

BACKGROUND: We performed an experimental study on 46 male rats to evaluate the vitality of superficial inferior epigastric neurovenous flaps performed following different procedures. METHODS: Rats were divided into 5 groups: A (n=6), B (n=10), C (n=10), D (n=10) and E (n=10). On each rat a hemi-abdominal flap based on the superficial inferior epigastric pedicle was raised. In group A the flap was sutured into its original position, isolating it from underlying tissues by a latex glove patch. In group B an arteriectomy of the superficial inferior epigastric artery was performed. In group C the superficial inferior epigastric artery was sectioned at its origin, without dissecting it out of the pedicle. In group D and E the same procedures performed respectively in group B and C were followed, but the epigastric pedicles were immediately explanted for optic microscope observation. Flap vitality in groups A, B and C was checked after 7 days. RESULTS: Flaps in group A appeared completely vital: the glove did not interfere with flap survival. All flaps in group B looked necrotic. In group C, 9 flaps survived completely and 1 flap underwent complete necrosis. Pedicle specimens of the viable flaps (group C) were explanted for observation under the optic microscope. Each specimen from groups C, D, E revealed a rich vascular plexus in the connective tissue around the pedicle. Seven days after surgery, neo-microangiogenesis was evident. CONCLUSIONS: The results witness the importance of perivenous and perineural arterioles for neurovenous flaps survival, also considering the adaptive increase in capillary development in the days following surgery.

A case of life-threatening sepsis after breast augmentation by fat injection.

A case is presented in which an aesthetic breast augmentation by fat injection led a young woman to a life-threatening sepsis due to bilateral mammary abscesses. Immediate and late complications of this procedure are considered; infection is the frightful complication that can lead to septic shock, affecting survival, aesthetic outcome, and reconstruction possibilities of the patient's breasts.

A placebo controlled clinical trial investigating the efficacy of a homeopathic after-bite gel in reducing mosquito bite induced erythema.

A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One bite was treated with the homeopathic after-bite gel, another bite with a placebo gel which was identical in appearance and smell to the homeopathic after-bite gel, and the third bite remained untreated. Immediately after the bites and 1, 3, 6, 26 and 31 hours post-bite, the length and width of the erythema were measured with a calliper, and photographs were taken of the bite sites from which the size of the erythema was subsequently determined. This was followed by assessment of the extent of itching with a verbal analogue scale, and finally treatment took place. For each spot the total erythema was calculated as the area under the plotted curve of the erythema at different time points (mm2*h) and the total sum of the itch scores was determined. For the bites treated with the homeopathic after-bite gel the median total erythema was 10.500 mm2*h. For the spots treated with the placebo gel and the untreated spots the median total erythema was 12.900 mm2*h and 13.300 mm2*h, respectively. The difference between the spots treated with the homeopathic after-bite gel and the untreated spots came close to significance (two-tailed P = 0.06), which was not the case for the difference between the spots treated with the homeopathic after-bite gel and the spots treated with placebo gel (P = 0.13). After pooling the data of a very similar previous pilot study and the present study (ntotal = 83), the homeopathic after-bite gel was significantly superior to no treatment (two-tailed P = 0.003) as well as to placebo gel (two-tailed P = 0.03). Comparing itching after the three treatments, no significant differences could be demonstrated. The extent of itching was positively correlated with the area of the erythema (r = 0.63). Treatment of mosquito bites with the homeopathic after-bite gel will reduce the erythema compared to no treatment. Comparison with the placebo gel suggests it is the plant extracts which are the active components of this gel.