Use of Platelet-rich Plasma for Vulvovaginal Autoimmune Conditions Like Lichen Sclerosus.

BACKGROUND: Lichen sclerosus (LS) is an inflammatory dermatosis with autoimmune pathogenesis. Although relatively common, its true incidence is unknown and likely underestimated. LS is usually anogenital, but in around 10% of patients, it can present as extragenital lesions. Continuous administration of topical corticosteroids is the mainstay of medical treatment. Other treatments are available but are only occasionally prescribed along with or instead of topical steroids. Injection of platelet-rich plasma (PRP) into affected areas has been reported to result in the regeneration of normal skin. In this study, we aimed to evaluate the safety, symptom resolution, and objective improvement in patients with autoimmune condition like genital LS after treatment with PRP. METHODS: Over a 2-year period at FBW Gynaecology Plus, we had a total of 28 patients with confirmed LS on biopsy, unresponsive to topical steroid treatment. After acquiring informed consent, patients' own blood was centrifuged on site and injected under local anesthesia to the external genitalia. RESULTS: Almost all of our patients showed clinical improvement in the size of their lesions, and in 8 cases, lesions totally disappeared after treatment with PRP. Symptoms disappeared in 15 of the 28 patients after treatment, with no need for further steroid therapy in 23 patients. Thirteen women experienced partial symptom relief. CONCLUSIONS: Based on our limited findings, we hypothesize that PRP presents a potential alternative to topical steroids for treatment of vulvovaginal autoimmune conditions such as LS. A larger pilot and/or randomized controlled trial study is required to evaluate this finding further.

Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner.

In bone, depletion of osteoclasts reduces bone formation in vivo, as does osteal macrophage depletion. How osteoclasts and macrophages promote the action of bone forming osteoblasts is, however, unclear. Since recruitment and differentiation of multi-potential stromal cells/mesenchymal stem cells (MSC) generates new active osteoblasts, we investigated whether human osteoclasts and macrophages (generated from cord blood-derived hematopoietic progenitors) induce osteoblastic maturation in adipose tissue-derived MSC. When treated with an osteogenic stimulus (ascorbate, dexamethasone and ß-glycerophosphate) these MSC form matrix-mineralising, alkaline phosphatase-expressing osteoblastic cells. Cord blood-derived progenitors were treated with macrophage colony stimulating factor (M-CSF) to form immature proliferating macrophages, or with M-CSF plus receptor activator of NFκB ligand (RANKL) to form osteoclasts; culture medium was conditioned for 3 days by these cells to study their production of osteoblastic factors. Both osteoclast- and macrophage-conditioned medium (CM) greatly enhanced MSC osteoblastic differentiation in both the presence and absence of osteogenic medium, evident by increased alkaline phosphatase levels within 4 days and increased mineralisation within 14 days. These CM effects were completely ablated by antibodies blocking gp130 or oncostatin M (OSM), and OSM was detectable in both CM. Recombinant OSM very potently stimulated osteoblastic maturation of these MSC and enhanced bone morphogenetic protein-2 (BMP-2) actions on MSC. To determine the influence of macrophage activation on this OSM-dependent activity, CM was collected from macrophage populations treated with M-CSF plus IL-4 (to induce alternative activation) or with GM-CSF, IFNγ and LPS to cause classical activation. CM from IL-4 treated macrophages stimulated osteoblastic maturation in MSC, while CM from classically-activated macrophages did not. Thus, macrophage-lineage cells, including osteoclasts but not classically activated macrophages, can strongly drive MSC-osteoblastic commitment in OSM-dependent manner. This supports the notion that eliciting gp130-dependent signals in human MSC would be a useful approach to increase bone formation.

Risk factors for recurrent Mycobacterium ulcerans disease after exclusive surgical treatment in an Australian cohort.

OBJECTIVE: To describe risk factors for recurrence after exclusive surgical treatment of Mycobacterium ulcerans infection. DESIGN, SETTING AND PARTICIPANTS: Prospective observational cohort study of all M. ulcerans cases managed with surgery alone at Barwon Health, a tertiary referral hospital, from 1 January 1998 to 31 December 2011. A random-effects Poisson regression model was used to assess rates and associations of treatment failure. MAIN OUTCOME MEASURES: Rates of treatment failure and rate ratios (RRs) for factors associated with treatment failure. RESULTS: Of 192 patients with M. ulcerans infection, 50 (26%) had exclusive surgical treatment. Median age was 65.0 2013s (interquartile range [IQR], 45.5-77.7 2013s), and median duration of symptoms was 46 days (IQR, 26-90 days). There were 20 recurrences in 16 patients. For first lesions, the recurrence incidence rate was 41.8 (95% CI, 25.6-68.2) per 100 person-2013s, and median time to recurrence was 50 days (IQR, 30-171 days). Recurrence occurred ≤ 3 cm from the original lesion in 13 cases, and > 3 cm in nine. On univariable analysis, age ≥ 60 2013s (RR 13.84; 95% CI, 2.21-86.68; P < 0.01), distal lesions (RR, 20.43; 95% CI, 1.97-212.22; P < 0.01), positive histological margins (RR, 21.02; 95% CI, 5.51-80.26; P < 0.001), immunosuppression (RR, 17.97; 95% CI, 4.17-77.47; P < 0.01) and duration of symptoms > 75 days (RR, 10.13; 95% CI, 1.76-58.23; P = 0.02) were associated with treatment failure. On multivariable analysis, positive margins (RR, 7.72; 95% CI, 2.71-22.01; P < 0.001) and immunosuppression (RR, 6.45; 95% CI, 2.42-17.20; P = 0.01) remained associated with treatment failure. CONCLUSIONS: Recurrence rates after exclusive surgical treatment of M. ulcerans disease in an Australian cohort are high, with increased rates associated with immunosuppression or positive histological margins.

Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study.

BACKGROUND: The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia. METHODOLOGY/PRINCIPAL FINDINGS: Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was 62 years (range 3-94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p<0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27-2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases. CONCLUSIONS: Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.

Outcomes for Mycobacterium ulcerans infection with combined surgery and antibiotic therapy: findings from a south-eastern Australian case series.

OBJECTIVE: To describe the effect of antibiotics on outcomes of treatment for Buruli or Bairnsdale ulcer (BU) in patients on the Bellarine Peninsula in south-eastern Australia. DESIGN: Observational, non-randomised study with data collected prospectively or through medical record review. PATIENTS AND SETTING: All 40 patients with BU managed by staff of Barwon Health's Geelong Hospital (a public, secondary-level hospital) between 1 January 1998 and 31 December 2004. MAIN OUTCOME MEASURES: Epidemiology, clinical presentation, diagnosis, treatment and clinical outcomes. RESULTS: There were 59 treatment episodes; 29 involved surgery alone, 26 surgery plus antibiotics, and four antibiotics alone. Of 55 episodes where surgery was performed, minor surgery was required in 22, and major surgery in 33. Failure rates were 28% for surgery alone, and 19% for surgery plus antibiotics. Adjunctive antibiotic therapy was associated with increased treatment success for lesions with positive histological margins (P < 0.01), and lesions requiring major surgery for treatment of a first episode (P < 0.01). The combination of rifampicin and ciprofloxacin resulted in treatment success in eight of eight episodes, and no patients ceased therapy because of side effects with this regimen. CONCLUSIONS: Adjunctive antibiotic therapy may increase the effectiveness of BU surgical treatment, and this should be further assessed by larger randomised controlled trials. The combination of rifampicin and ciprofloxacin appears the most promising.