Symmetrical peripheral gangrene and disseminated intravascular coagulation

Symmetrical peripheral gangrene (SPG) is a rare syndrome associated with a multitude of underlying medical problems. We are adding three cases of SPG to the medical literature, all of which had disseminated intravascular coagulation (DIC). Each had an underlying illness that, to our knowledge, has not been previously associated with SPG: Hodgkin's lymphoma, Escherichia coli urinary tract infection with septicemia, and polymyalgia rheumatica. Review of the medical literature shows a high association between SPG and DIC. Symmetrical peripheral gangrene should therefore be considered a cutaneous marker of DIC. Early recognition and treatment of the underlying medical problem and DIC could be lifesaving.     

Conservative management of distal leg necrosis in lung transplant recipients

Critical limb ischemia (CLI) with distal leg necrosis in lung transplant recipients (LTR) is associated with a high risk for systemic infection and sepsis. Optimal management of CLI has not been defined so far in LTR. In immunocompetent individuals with leg necrosis, surgical amputation would be indicated and standard care. We report on the outcome of four conservatively managed LTR with distal leg necrosis due to peripheral arterial disease (PAD) with medial calcification of the distal limb vessels. Time interval from lung transplantation to CLI ranged from four years (n = 1) to more than a decade (n = 3). In all cases a multimodal therapy with heparin, acetylsalicylic acid, iloprost and antibiotic therapy was performed, in addition to a trial of catheter-based revascularization. Surgical amputation of necrosis was not undertaken due to fear of wound healing difficulties under long-term immunosuppression and impaired tissue perfusion. Intensive wound care and selective debridement were performed. Two patients developed progressive gangrene followed by auto-amputation during a follow-up of 43 and 49 months with continued ambulation and two patients died of unrelated causes 9 and 12 months after diagnosis of CLI.In conclusion, we report a conservative treatment strategy for distal leg necrosis in LTR without surgical amputation and recommend this approach based on our experience.     

Dipeptidyl‐peptidase IV inhibitors (DPP4i)‐associated bullous pemphigoid: Estimating the clinical profile and exploring intraclass differences

Data regarding the clinical characteristics of patients with dipeptidyl‐peptidase IV inhibitors (DPP4i)‐associated BP is inconclusive. We aimed to characterize the clinical features of patients with DPP4i‐associated BP, and to assess whether there are phenotypic differences associated with different agents belonging to the DPP4i class. A retrospective prevalence study was performed, including all consecutive patients diagnosed with BP throughout the years 2000 to 2019. The study included 397 patients with BP, of whom 58 (14.6%) were DPP4i‐associated. Compared to other patients with BP, patients with DPP4i‐associated BP had a more prominent male preponderance (60.3% vs 41.0%; P = .006), presented more frequently with extensive disease (60.3% vs 46.3%; P = .049), had greater truncal (96.6% vs 85.5%; P = .019) and cephalic (51.7% vs 33.6%; P = .008) involvement, and had less frequent peripheral eosinophilia (25.9% vs 51.9%; P < .001). Compared to patients with vildagliptin‐associated BP, those with linagliptin‐associated BP were managed by higher dosage of systemic corticosteroids in order to achieve disease control (prednisone > 1 mg/kg: 68.2% vs 40.0%; P = .046). In conclusion, DPP4i‐associated BP seems to have a unique clinical profile characterized by male predominance, extensive disease, truncal and cephalic involvement, and less peripheral eosinophilia. Linagliptin may be associated with a harder course necessitating more aggressive therapy.     

Paraneoplastic acral vascular syndrome: epidemiologic features,clinical manifestations,and disease sequelae

BACKGROUND: Acral vascular syndromes associated with malignancy have rarely been reported. OBJECTIVE: Our purpose was to assess the clinical and evolving features of paraneoplastic acral vascular syndromes. Patients and Methods: Two cases of paraneoplastic gangrene are described and analyzed together with previously reported cases identified by a MEDLINE search. RESULTS: Among the 68 patients identified, 40 had gangrene, 16 had acrocyanosis, and 12 had Raynaud's phenomenon. The male to female ratio was 0.89; median age was 59 years. Fingers were affected in 94%. Adenocarcinomas were the predominant associated malignancies (41%), and metastases were observed in 41%. The acral vascular syndromes in 48% of the patients definitively regressed after tumor treatment. Forty-four percent of the patients died within 2 years. A favorable cutaneous outcome was obtained with prostacyclin infusions in 6 patients. CONCLUSION: A neoplastic origin of acral vascular syndrome should be considered in elderly patients, especially men, in the absence of usual causative conditions.     

Measurement of a possible patch‐testing outcome indicator

Background: Clinical performance measurements often employ outcome indicators to express the extent to which health services achieve a given clinical result. Objective: The objective of our study was to develop an outcome indicator of patch testing. We identified and measured as a possible indicator the ratio of patients with allergic and/or photo‐allergic contact dermatitis clinically cured/improved as a result of identification of relevant allergens. Patients/Methods: Patients with positive reactions considered relevant to their current dermatitis were interviewed by telephone 2 months after patch/photo‐patch testing in order to assess their clinical outcome in relation to the recommended elimination of supposedly relevant allergens. Results: Over a 4‐year period positive reactions were seen in 1397 out of 2857 tested patients. Relevance was considered current in 578 subjects, and 506 of them were interviewed. Remission/significant improvement following allergen(s) contact avoidance was reported by 431 patients, the outcome indicator (431/506) thus scoring 85.2%. Among the 75 patients who reported no improvement, 41 had not avoided contact with the offending substance(s), 17 had other persistent concomitant skin conditions, and 17 were unchanged despite elimination of the alleged relevant allergens. Conclusions: The ratio of relevantly patch‐test‐positive patients resolved/improved after allergen avoidance is a useful patch‐testing outcome indicator.     

Arterial thrombosis in scleroderma

Clinical and pathological observations are presented on five patients with scleroderma who developed thrombosis of a major vessel. Three died following intestinal infarction or limb gangrene and two had digit or extremity amputation. Severe intimal thickening of major arteries with thrombus formation was noted but no significant abnormality was found in the clotting activity of the blood. Histochemical studies in three cases suggested a reduction of fibrinolytic activity at the site of thrombosis in the diseased vessels. These studies support the view that the vascular system is profoundly altered in scleroderma and may play an important role in some manifestations of the disease.     

严重下肢缺血性坏疽伴感染导致肺水肿的临床研究

目的分析严重下肢末端缺血坏疽伴感染患者发生肺水肿的现象及原因。方法回顾性分析11例典型下肢缺血坏疽伴感染患者，在截肢术前后全身炎症状态及肺水肿的现象及转归。结果上述患者在出现全身炎症反应时，体温高达38．5℃以上，肺部满布中细湿哕音甚至哮鸣音，呼吸困难明显，广谱抗生素治疗效果不佳，但在患肢高位截肢后，肺部症状体征在数小时内很快缓解，体温、血象及全身情况迅速好转。结论下肢末端缺血坏疽伴感染患者发生肺水肿的原因，主要是坏死及感染组织毒素吸收后，刺激引起全身炎症介质释放所致，也与肺部血管通透性增加有关。此时，坚决果断的患肢高位截肢手术，是挽救患者生命的最重要措施之一。     

Clinical and pathological characteristics of melanoma: a population‐based study in a French regional population

Background Although incidence and mortality data are numerous, population‐based studies including clinical and pathological characteristics of melanoma are rare. Objectives To describe the characteristics of melanoma in a rural French region during 2004–2008 and to identify differences according to age, gender and geographical areas. Methods Pathology reports of cutaneous melanomas diagnosed in residents from the Champagne‐Ardenne region during 2004–2008 were anonymously collected from pathology laboratories. Demographic, clinical and pathological data were extracted and analysed by experts, including dermatologists, pathologists and epidemiologists. Results One hundred and seventy‐seven in situ melanomas were diagnosed in 177 patients (female/male ratio : 1.72). Patients with head and neck in situ melanomas were older than patients with melanomas in other locations (72 vs. 54 years; P < 0.0001). Six hundred and sixty‐one invasive melanomas were diagnosed (female/male ratio : 1.26), corresponding to an annual incidence rate of 6.3/100 000. Male patients had thicker and more frequently ulcerated tumours. The location widely varied between genders, involving the trunk in 47% of male patients and the lower limb in 48% of female patients. Older patients had thicker and more advanced melanomas, with a more frequent head and neck location. Nodular, acral lentiginous and unclassified melanomas were much thicker than superficial spreading and lentigo maligna melanomas (4.37 vs. 1.33 mm, P < 0.0001). Primary melanomas of advanced stages were more frequent in one of the four districts of the study area. Overall, the mean Breslow thickness (2.02 mm) was much higher than that previously observed in other regions of north‐eastern France (1.59 mm). Conclusions Information and screening campaigns should particularly target rural areas, males, older people and focus on nodular, acrolentiginous and unclassified subtypes.     

Folliculotropic mycosis fungoides: Clinical characteristics,treatments, and long‐term outcomes of 53 patients in a tertiary hospital

Folliculotropic mycosis fungoides (FMF) is characterized by a broad clinical spectrum and worse prognosis compared to classical MF. This study aimed to evaluate the clinical characteristics, treatment modalities and long‐term outcome and risk factors for progression and survival of FMF patients. We conducted a single‐center retrospective study and reviewed 53 patients diagnosed with FMF between 1990 to 2019 in a referral center at Ankara University, Turkey. Regarding to stage at diagnosis, 24 patients (45.3%) had advanced‐stage disease (≥IIB). Follicular papules was observed in 66% and alopecia in 49.1% of the cases. Forty‐three patients (81.1%) suffered from pruritus. The majority of the patients (92.4%) had at least one systemic therapy. Complete remission was achieved in 24.5% of the patients. The median time of overall survival (OS) was 50 months (range 9‐324 months) and 5‐year and 10‐year OS was 83% and 69%, respectively. Twenty‐eight (52.3%) patients progressed to more advanced stages and seven (13.2%) patients died due to MF during the follow‐up period. FMF is associated with a progressive course and in most patients, skin‐directed therapies were found to be inefficient to control the disease and multiple systemic therapeutic agents were required to control the disease.     

Aggressive digital papillary adenocarcinoma: a review

Vigorous treatment of aggressive digital papillary adenocarcinoma (ADPA), including amputation, has been recommended by most authors, but the appropriateness and effectiveness of excision as an alternative to amputation has not been systematically evaluated. To evaluate the appropriateness and effectiveness of excision as an alternative to amputation in the treatment of ADPA, we reviewed the clinical presentations, treatments and patient outcomes presented in case reports on ADPA available on Ovid MEDLINE. We also assessed the results of immunohistochemical staining for proliferation markers in one patient in order to explain the nonaggressive nature of ADPA noted in that patient. Except for the duration of lesions, there was no significant difference in clinical outcome between the excision and amputation groups. We also found that p63 may be a useful marker for distinguishing primary ADPA from metastatic adenocarcinomas. In addition, the intensity of Ki67 expression in tumour cells may be a marker of aggressive behaviour and thus be helpful in therapeutic decision‐making. Wide excision with or without sentinel lymph‐node biopsy is a feasible alternative to amputation. It should be considered in patients who present with a long‐standing history of ADPA without evidence of underlying bone invasion or distant metastasis and with low‐intensity expression of proliferation markers.     

Cutaneous lymphocyte‐associated antigen as a novel predictive marker of TNF‐alpha inhibitor biological therapy in psoriasis

A considerable number of patients with psoriasis show secondary resistance during long‐term TNF‐alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte‐associated antigen (CLA) was investigated. Thirty‐eight severe patients with psoriasis were treated for a 24‐week‐long study period. Clinical responsiveness (PASI) and changes in flow cytometry–measured peripheral lymphocyte CLA expression (week 0–2–6) were statistically analysed. Regarding 24‐week‐long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF‐alpha inhibitor therapy in psoriasis.     

Fournier gangrene: description of 37 cases and analysis of associated health care costs

Background and objectivesFournier gangrene is a urological emergency associated with a high mortality. It is a necrotizing fasciitis caused by polymicrobial infection originating in the anorectal or genitourinary area. The aim of this study was to analyze the epidemiological and clinical characteristics of Fournier gangrene along with the variables that influence disease course and mortality in patients treated in our department.Material and methodsWe carried out a retrospective study of 37 patients diagnosed with Fournier gangrene between January 2001 and October 2010.ResultsAll of the patients were men, 43.2% had diabetes, and the mean age of the patients was 57.68 years. Statistically significant differences were observed between the age of surviving patients and that of patients who died (55.8 and 69.6 years, respectively). The mean hospital stay was 27.54 days and 32.4% of patients required admission to the intensive care unit. Etiology was unknown in 39.8% of cases. Polymicrobial infection was observed in 59.5% of cases. The mean health care cost associated with a patient diagnosed with Fournier gangrene admitted to intensive care and requiring at least 1 procedure in the operating room was €25 108.67. Mortality was 13.5%. Based on analysis of individual comorbid conditions, only ischemic heart disease displayed a statistically significant association with mortality due to Fournier gangrene; ischemic heart disease was also associated with longer hospital stay.ConclusionsFournier gangrene is associated with high mortality despite appropriate early treatment. Although the condition is infrequent, the high associated health care costs suggest that primary and secondary prevention measures should be implemented.     

Photodynamic therapy using topical 5‐aminolaevulinic acid vs. surgery for basal cell carcinoma

Background Photodynamic therapy (PDT) is an attractive modality for the treatment of BCC, based on its generally favorable efficacy, adverse effect profile and its excellent cosmetic outcome. Objectives The purpose of the study is to compare the efficacy and cosmetic outcome of photodynamic therapy with topical 5‐aminolaevulinic acid (ALA‐PDT) vs. simple excision surgery for superficial and nodular basal cell carcinoma (BCC). Methods A total of 72 patients, 32 with 48 lesions, were treated with ALA‐ PDT, and 40 with 46 lesions treated by excision were included in this prospective, comparative, controlled, clinical study. The patients have been followed for 16–37 months (mean 25 months). The PDT was performed in combination with 5‐aminolaevulinic acid twice, one month apart. Surgical excision was performed under local anesthesia with a 3‐mm margin, followed by histological examination. The cosmetic outcome was evaluated by the physician according to a 4‐point scale. Results Overall 94 BCC were treated. Complete healing rates did not differ significantly between groups, P = 0.64 (46/48 [95.83%] lesions treated with PDT vs. 44/46 [95.65%] lesions with surgery). In the first 12 months of follow‐up, 4 lesions had recurred, 2 of which were in the PDT group while 2 lesions after surgery. The mean follow‐up was 25 months. The recurrence rate in the ALA‐PDT group was 4.16% vs. 4.34% in the surgery group, p = 0.64. The cosmetic outcome was superior for ALA‐PDT at all time points. At 12 months, 100% lesions treated with ALA‐PDT had an excellent or good cosmetic outcome, according to the investigator, compared with 88.86% with surgery, P = 0.01. Conclusion ALA‐PDT offers a similarly high efficacy, and a better cosmetic outcome than simple excision surgery in the treatment of BCC.     

Effect of mitotic density on the probability of survival of patients with thin (less than or equal to 1.5 mm) melanomas

Our studies dealt with the prognostic significance of the mitotic count for patients with thin (less than or equal to 1.5 mm) melanoma. We determined the mitotic rate of 50 patients who had died of melanoma thinner than 1.5 mm within 8 years (short-term survivors). The specimens were examined by means of a rectangular visual field; thus we could calculate the mitotic count to the square mm of the tumor surface. This outcome was compared to the mitotic rate of 50 long-term survivors who had not died within 8 years and who corresponded to the first group with regard to sex, tumor thickness, as well as tumor site. In both groups, at least 15% of the melanomas did not show any mitotic figure. With females, the average mitotic values were identical in both groups (1.1 vs. 1.15). In males, however, short-term survivors revealed a significantly (p less than 0.001) higher mitotic count (2.2) than long-term survivors (0.75).     

Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression

Background Multimarker quantitative real‐time polymerase chain reaction (qRT‐PCR) represents an effective method for detecting circulating tumour cells in the peripheral blood of patients with melanoma. Objectives To investigate whether the phenotype of circulating melanoma cells represents a useful indicator of disease stage, recurrence and treatment efficacy. Methods Peripheral blood was collected from 230 patients with melanoma and 152 healthy controls over a period of 3 years and 9 months. Clinical data and blood samples were collected from patients with primary melanoma (early stages, 0–II, n = 154) and metastatic melanoma (late stages, III–IV, n = 76). Each specimen was examined by qRT‐PCR analysis for the expression of five markers: MLANA, ABCB5, TGFβ2, PAX3d and MCAM. Results In total, 212 of the patients with melanoma (92%) expressed markers in their peripheral blood. Two markers, MLANA and ABCB5, had the greatest prognostic value, and were identified as statistically significant among patients who experienced disease recurrence within our study period, being expressed in 45% (MLANA) and 49% (ABCB5) of patients with recurrence (P = 0·001 and P = 0·031, respectively). For patients administered nonsurgical treatments, MCAM expression correlated with poor treatment outcome. Conclusions Circulating tumour cells were detectable at all stages of disease and long after surgical treatment, even when patients were considered disease free. Specifically, expression of ABCB5 and MLANA had significant prognostic value in inferring disease recurrence, while MCAM expression was associated with poor patient outcome after treatment, confirming multimarker qRT‐PCR as a potential technique for monitoring disease status.     

Field treatment of facial and scalp actinic keratoses with photodynamic therapy: survey of patient perceptions of treatment satisfaction and outcomes

Background: Diffuse field change with actinic keratoses (AK) is a ubiquitous skin disease in Australia, with potential for malignant transformation. We report on 35 consecutive patients who had field therapy with single session photodynamic therapy (PDT) using 1 h incubation time for 5‐aminolevulinic acid (5‐ALA) or 3 h for methyl‐aminolevulinate (MAL). Methods: We retrospectively telephone surveyed our patient cohort regarding their satisfaction and perceptions of the effectiveness, side‐effect profile and benefits of PDT. We also reviewed all patients' notes for significant side‐effects. Results: Sixty‐nine per cent (n = 24/35) of patients responded to the telephone survey; 66% (n = 16/24) of the respondents reported good clearance of AK and claimed a good cosmetic outcome. All respondents reported moderate or severe pain (42% and 58%, respectively) during the illumination phase. Twenty per cent of all patients treated had suffered from one or more of the following side‐effects: pustulation; severe erythema; and skin erosions. Conclusions: Overall, our results compared favourably with previously published studies using 5‐ALA or MAL PDT. However, our patient cohort experienced a greater side‐effect profile. This may have been due to our patients having greater disease burden compared to other studies and possibly due to our use of topical retinoids prior to PDT in selected patients.     

Conservative surgical management of subungual (matrix derived) melanoma: report of seven cases and literature review

Background Subungual melanoma (SUM) is a rare entity, comprising approximately 0·7–3·5% of all melanoma subtypes. SUM histopathologically belongs to the acral lentiginous pathological subtype of malignant melanoma. Its diagnosis is helped by dermoscopy but pathological examination of doubtful cases is required. Classical management of SUM is based on radical surgery, namely distal phalanx amputation. Conservative treatment with nonamputative wide excision of the nail unit followed by a skin graft has been insufficiently reported in the medical literature even though it is performed in many centres. Objectives To report a series of patients with in situ or minimally invasive SUM treated by conservative surgery, to investigate the postoperative evolution and to evaluate the outcome with a review of the literature. Methods We performed a retrospective extraction study from our melanoma register of all patients with in situ and minimally invasive SUM treated with conservative surgery in the University Hospital Department of Dermatology, Lyon, France from 2004 to 2009. The patient demographics, disease presentation, delay to diagnosis, histopathology and postoperative evolution were reviewed. Results Seven cases of SUM treated as such were identified in our melanoma database. All cases had a clinical presentation of melanonychia striata. The mean delay to diagnosis was 2 years. Surgical excision of the entire nail unit with a 5–10 mm safety margin without bone resection followed by full‐thickness skin graft taken from the arm was performed in all cases. No recurrence was observed with a mean follow‐up of 45 months. Functional results were found satisfactory by all patients and their referring physicians. Sixty‐two other cases have been found in the literature and are also discussed. Conclusions Conservative surgical management in patients with in situ or minimally invasive SUM is a procedure with good cosmetic and functional outcome and, in our cases as well as in the literature, the prognosis is not changed.     

Improvement in early diagnosis of Japanese spotted fever by using a novel Rick PCR system

Rickettsia diseases, including Japanese spotted fever (JSF), are serious infections. Delayed diagnosis occasionally results in life‐threatening liver disorders and disseminated intravascular coagulation (DIC). Because of the shortness of the latent period, serological diagnosis is not preferable for early diagnosis of JSF. Until now, a polymerase chain reaction (PCR)‐based diagnosis method has been used for early diagnosis, and the sensitivity reaches as high as 90% using skin biopsy samples as we previously reported. On the other hand, the sensitivity of the same PCR method using blood samples is limited at less than 50%. In the present study, using peripheral blood samples, we developed a novel diagnostic method for JSF using a Rick PCR system with original PCR primers, showing improved sensitivity compared with the conventional nested PCR. It may constitute a preferable diagnostic tool for early and sensitive diagnosis of Rickettsia infection.