The importance of serum creatine phosphokinase level in the early diagnosis and microbiological evaluation of necrotizing fasciitis

BACKGROUND: Necrotizing fasciitis (NF) due to group A beta-haemolytic streptococci (GAS) is a rare but still life-threatening soft-tissue infection characterized by rapidly spreading necrosis of the muscle fascia and of the surrounding tissues. NF other than that due to GAS involves the participation of one or more anaerobes and/or of non-group A streptococci, Staphylococcus aureus, enteric organisms, and may be associated with a better outcome. Early diagnosis and treatment, consisting of surgical debridement along with appropriate antibiotic therapy, are required to reduce morbidity and mortality rates. OBJECTIVES: The aim of the study was to analyse the clinical and laboratory findings of patients with GAS NF and with non-GAS NF, and to identify which characteristics could help to diagnose NF in the early stages of infection. METHODS: We retrospectively analysed the clinical and laboratory findings of 43 cases of GAS and non-GAS NF that occurred in Belgium (n = 32) and at Saga Medical School (Japan) (n = 11) between May 1984 and December 2001. RESULTS: GAS NF more frequently occurred in previously healthy individuals than NF due to other pathogens (P < 0.05) but was associated with a poorer prognosis. Both for patients with GAS NF and with non-GAS NF, the first clinical manifestations often suggested a diagnosis of erysipelas or cellulitis and rarely evoked the correct diagnosis (12% and 15% of the cases, respectively). However, we found that creatine phosphokinase (CPK) values were far higher in patients with GAS NF than in those with non-GAS NF. CONCLUSIONS: Our data suggest that GAS may exert particular tropism and/or toxicity for muscle, responsible for early muscle necrosis. This indicates that elevated levels of CPK in a patient with erysipelas or cellulitis-like symptoms should clearly prompt the clinician to exclude the diagnosis of GAS NF.     

Necrotizing fasciitis: pathophysiology and treatment

Necrotizing fasciitis (NF) is a life-threatening bacterial infection causing necrosis of the fascia, underlying skin, and vasculature. NF spreads rapidly, making immediate diagnosis important for survival. Treatment may involve the administration of several broad-spectrum antibiotics, surgical debridement, and skin grafting. In the following two articles, the pathophysiology, medical management, and nursing care of patients are discussed. An in-depth model care plan illustrates the complexity of the disease and its treatment.     

Necrotizing fasciitis caused by Cryptococcus neoformans in a patient with pemphigus vegetans

Cryptococcosis occurs most often in immunocompromised people. The cutaneous features of cryptococcosis include papules, pustules, nodules, subcutaneous swelling, abscesses, molluscum contagiosum‐like or tumour‐like lesions, cellulitis, blisters, ulcers and very rarely, necrotizing fasciitis (NF). NF is a destructive soft‐tissue infection that is most typically caused by group A streptococci or by a combination of facultative and anaerobic bacteria. We present the case of a 55‐year‐old woman with pemphigus vegetans, who developed cryptococcal NF in the legs. She had been treated with immunosuppressants including plasmapheresis and pulse therapy with steroid and cyclophosphamide. Cryptococcal NF localized to the legs is very rare. Because diagnosis and treatment of cryptococcal infection is often delayed, clinicians should be aware of the possibility of cryptococcal infection when antibacterial therapy is not effective in an immunocompromised patient.     

Necrotizing fasciitis and cardiac catheterization

Necrotizing fasciitis (NF) is an uncommon, life-threatening soft tissue infection characterized by rapidly spreading inflammation and necrosis of the skin, subcutaneous tissue, and fascia. We report a case of NF as a complication of cardiac catheterization. Familiarity with this entity may lead to earlier diagnosis and initiation of appropriate therapy.     

Coagulation and fibrinolytic systems during the course of erysipelas and necrotizing fasciitis and the effect of heparin

Necrotizing fasciitis (NF) is a grave infection of the skin leading to gangrene of the integument and often having a complicated and prolonged course. Studies on blood coagulation and fibrinolysis were done in 15 patients with NF and compared with 5 cases of erysipelas (E). In both conditions local fibrin deposition occurred initially in their course, but it was quantitatively more pronounced in NF than in E. Fibrinolysis decreased and stayed low at the site of NF up to 5 months (median) after discharge from hospital. Fibrinogen and activities of several plasma serine proteinases modifying coagulation were increased during the course of both diseases and even at the follow-up. Factor XII was decreased during the first week in E but a transient drop was present in NF only on days 3 and 4. The treatment of NF consists of high doses of appropriate antibiotics instituted early in its course. A beneficial effect of 300-500 IU heparin/kg/day was suggested from this open study. The hard induration preceding the appearance of skin gangrene was inhibited, if heparin was given early in the course of NF. We conclude that the enhanced fibrin deposition and vascular occlusions in the skin are the basis for most complications present in NF.     

Group a beta-haemolytic streptococcal necrotising fasciitis: early diagnosis and clinical features

Necrotising fasciitis (NF) due to group A beta-haemolytic streptococci (GAS) is a rare but still life-threatening soft-tissue infection characterised by rapidly spreading inflammation and subsequent necrosis of the muscle fascia and of the surrounding tissues. Previous studies have emphasised that the outcome of patients with NF depends essentially on early diagnosis and treatment, consisting of extensive surgical debridement, along with appropriate antibiotic therapy. However, one of the striking features of the published series of GAS NF is that there was a delay in diagnosis in several cases, which underscores the difficulty of the early diagnosis of the condition. The goal of this article was to review the clinical features and diagnostic tools that could facilitate the early recognition of GAS NF.     

Treatment of Nodular Fasciitis Occurring on the Face

BackgroundSurgical excision is generally recommended for the treatment of nodular fasciitis (NF) to rule out sarcoma. However, in cases of NF occurring on the face, the reported recurrence rate is higher and the surgical approach may result in considerable aesthetic concern.ObjectiveTo describe our experience with NF occurring on the face and evaluate the outcomes of surgical and nonsurgical methods of treatment.MethodsWe performed a retrospective review of 16 patients with NF on the face. The patients were treated with surgical excision or nonsurgical methods such as triamcinolone intralesional injection (TA ILI) and pinhole method with a carbon dioxide (CO₂) laser.ResultsAmong the 16 patients, surgical treatment was performed in 9 and recurrence occurred in 7 of these 9 patients (77.8%). The recurred lesions showed regression after repeated TA ILI. On the other hand, five patients underwent nonsurgical treatment after the histologic exclusion of malignancy. Their lesions showed regression after repeated pinhole treatment and TA ILI. In one case, NF spontaneously regressed. On a visual analogue scale, the nonsurgical approach showed superior results. However, the values were not statistically significant (6.90±1.56 vs. 5.61±1.36; p=0.163). The satisfaction level was lower in patients who experienced recurrence after surgical excision.ConclusionSurgical treatment for NF on the face showed a noticeable recurrence rate and resulted in scarring. Therefore, considering the possibility of spontaneous regression, the nonsurgical method can be considered as an alternative treatment option for NF on the face.     

Segmental neurofibromatosis

Three cases of segmental neurofibromatosis (NF) and one case of bilateral segmental NF are described. Previous cases described as segmental NF are reviewed and evaluated in light of Riccardi's rigid definition of segmental NF. The previously reported cases are then placed in four subgroups. Segmental NF may evolve into a generalized form over time. Also, this disorder may occur in a heritable manner, Genetic counseling of affected individuals must include these facts.     

Neurofibromatosis type 2 in an infant with multiple plexiform schwannomas as first symptom

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that is caused by inactivating mutations or a loss of both alleles in the NF2 tumor-suppressor gene. Bilateral vestibular schwannomas are considered to be the hallmark of this disease, with hearing loss and tinnitus which are caused by these tumors, usually presenting as the initial symptoms. In addition to other tumors and ocular findings, skin abnormalities also occur in NF2, however, they are not so characteristic as neurofibromatosis type 1 (NF1). We herein report a case of NF2 which occurred in a 5-year-old boy. He had multiple cutaneous tumors but did not have any symptoms related to vestibular schwannomas. He also had multiple depigmented spots. A histopathological examination revealed these tumors to be plexiform schwannomas; we therefore suspected NF2. As a result of magnetic resonance imaging with gadolinium enhancement, bilateral vestibular schwannomas were detected and a final diagnosis of NF2 was thus made. The association between NF2 and multiple depigmented spots is unknown, we therefore consider that multiple cutaneous plexiform schwannomas may strongly suggest an association with NF2.     

Treatment of pigmented lesions of neurofibromatosis 1 with intense pulsed-radio frequency in combination with topical application of vitamin D3 ointment

Cafe-au-lait spots and pigmented freckling are found in most of patients with neurofibromatosis 1 (NF1). Although many modalities have been used for treating the pigmented lesions, the response to treatment has been variable. Therefore, we performed the treatment of pigmented lesions with NF1 by intense pulsed-radio frequency (IPL-RF) in combination with topical application of vitamin D(3) ointment. Eight patients were treated in this study and the improvement was moderate to good in six cases (75%) although the response was relatively mild. Thus, results from our study indicate that IPL-RF irradiation in combination with topical application of vitamin D(3) ointment would be useful as new modalities, especially for treatment of numerous small pigmented lesions in patients with NF1. Although further studies with large groups of patients should be performed for a better conclusion, it could improve quality of life with NF1 patients who are concerned with serious cosmetic and social problems.     

Fibroblast dysfunction is a key factor in the non-healing of chronic venous leg ulcers

Chronic age-related degenerative disorders, including the formation of chronic leg wounds, may occur due to aging of the stromal tissues and ensuing dysfunctional cellular responses. This study investigated the impact of environmental-driven cellular aging on wound healing by conducting a comprehensive analysis of chronic wound fibroblast (CWF) behavior in comparison with patient-matched healthy skin normal fibroblasts (NF). The dysfunctional wound healing abilities of CWF correlated with a significantly reduced proliferative life span and early onset of senescence compared with NF. However, pair-wise comparisons of telomere dynamics between NF and CWF indicated that the induction of senescence in CWF was telomere-independent. Microarray and functional analysis suggested that CWFs have a decreased ability to withstand oxidative stress, which may explain why these cells prematurely senescence. Microarray analysis revealed lower expression levels of several CXC chemokine genes (CXCL-1, -2, -3, -5, -6, -12) in CWF compared with NF (confirmed by ELISA). Functionally, this was related to impaired neutrophil chemotaxis in response to CWF-conditioned medium. Although the persistence of non-healing wounds is, in part, due to prolonged chronic inflammation and bacterial infection, our investigations show that premature fibroblast aging and an inability to correctly express a stromal address code are also implicated in the disease chronicity.     

Multi-segmental neurofibromatosis

Neurofibromatosis (NF), one of the commonest phakomatoses, is characterized by varied clinical manifestations. Segmental NF is one of the uncommon subtypes of NF. We report a young adult presenting with asymptomatic skin lesions- neurofibromas and café-au-lait macules- over localized areas of the lower back, affecting more than one segment. None of the family members were found to have features of segmental NF. Segmental NF may be misdiagnosed as a birthmark or remain undiagnosed for long periods of time, as the patients are often asymptomatic. Moreover, the clinical features are highly variable and range from a small area of skin involvement to involvement over the entire half of the body. This variation is explained by the fact that segmental NF is thought to arise from a postzygotic NF1 gene mutation, leading to somatic mosaicism. We have also reviewed the relevant literature on this subject.     

Nosological considerations of the neurofibromatoses.

We are on the threshold of evaluating the NF1 and NF2 loci with respect to variant forms of the neurofibromatoses. Genetic mapping of NF1, gene cloning and characterization of its encoded product, neurofibromin, provides a framework for the evaluation of the variant forms of NF. This may also apply to NF2 variant forms in the near future. The mapping approach in evaluating variant forms of NF should begin with the rigorous clinical assessment of familial cases whereby the establishment of genetic linkage in families with overlap syndromes might determine if either NF1, NF2, or a separate locus is involved in the phenotype. Conditions mapping to the NF1 locus could then be screened for mutations in hopes of identifying the etiologies of the variant forms of NF. Mutation identification should provide a molecular-based classification scheme for the variant forms of NF, now tentatively divided into alternative and related forms. It is expected that the nosology of the neurofibromatoses will most certainly change as more is learned of the NF1 and NF2 loci.     

Necrotizing fasciitis caused by Staphylococcus epidermidis in a neonate with extremely low birthweight

Necrotizing fasciitis (NF) is a severe life‐threatening soft tissue infection characterized by rapidly spreading necrosis of the fascia and the subcutaneous tissue. The initial skin presentation ranges from minimal rash to cellulites. The lesions subsequently spread rapidly. Even with appropriate medical and surgical therapy, the mortality rate in NF is more than 50%. In cases of neonates, mortality rate is higher than that ratio. High index of suspicion, prompt aggressive surgery, appropriate antibiotics and supportive care are the mainstays of management in the newborn infant with NF. Herein, we report a case of invasive and mortal NF caused by Staphylococcus epidermidis in an infant with extremely low birthweight.     

Decreased prostaglandin E2 production by inflammatory cytokine and lower expression of EP2 receptor result in increased collagen synthesis in keloid fibroblasts

We investigated the metabolism of arachidonic acid in normal skin-derived fibroblasts (NF) as well as in keloid-derived fibroblasts (KF) in response to macrophage migration inhibitory factor (MIF), a pluripotent cytokine. We found that MIF enhanced cyclooxygenase-2 activity in NF more than in KF. Consistent with this finding, prostaglandin E(2) (PGE(2)), an antifibrogenic molecule, was more significantly increased in NF than in KF by MIF treatment. As regarding E prostanoid receptor 2, the level of expression was significantly lower in KF than in NF. On the other hand, Forskolin, a direct activator of adenylcyclase, decreased collagen synthesis in both NF and KF, which indicates that cAMP plays an important role in regulating collagen synthesis. As PGE(2) induces cAMP production, it is conceivable that increased collagen synthesis in KF might be owing to decreased PGE(2) and cAMP production. These findings may aid in the development of a therapeutic strategy for the regulation of collagen synthesis in keloid fibroblasts.     

Neurofibromatosis type 1 tumour suppressor gene expression is deficient in psoriatic skin in vivo and in vitro: a potential link to increased Ras activity

BACKGROUND: Neurofibromatosis type 1 (NF1) protein (neurofibromin) accelerates the inactivation of Ras-GTP in various cell types. Somatic mutations of the NF1 gene may lead to malignant transformation and uncontrolled proliferation. We have previously shown that NF1 protein expression is downregulated in psoriasis in vivo. OBJECTIVES: To study the functional expression and distribution of NF1 mRNA and protein in vivo and in psoriatic and normal keratinocyte cultures. METHODS: Immunohistochemistry and in situ hybridization were used to study NF1 gene and protein expression in psoriasis in vivo. Furthermore, Northern and in situ hybridizations, immunoblot and localization analyses were utilized to study NF1 mRNA and protein in vitro in keratinocyte cultures. RESULTS: NF1 tumour suppressor gene expression was reduced in lesional psoriatic skin compared with perilesional and normal skin in vivo. The in vitro results showed that the levels of NF1 mRNA and protein were reduced in cultured psoriatic keratinocytes during cellular differentiation even after multiple passaging of the cells. Moreover, cultured nonlesional psoriatic keratinocytes were almost equally defective as lesional cells with respect to NF1 expression. CONCLUSIONS: Our findings demonstrate that psoriatic keratinocytes maintain an altered phenotype and gene expression profile even when isolated from interaction with lymphocytes and fibroblasts, which are known to increase proliferation of keratinocytes. As NF1 protein is regarded as a Ras proto-oncogene regulator, the aberrant expression and distribution of NF1 protein and mRNA found in the present study may be causative to the previously described increased activation of Ras in psoriatic lesions, and relate to altered cellular behaviour.     

狼疮肾炎患者外周血单个核细胞NF-κB与糖皮质激素受体mRNA的表达

目的：检测狼疮肾炎患者单个核细胞核因子-κB（NF一κB）与糖皮质激素受体mRNA（GR-mRNA）的表达水平。方法：免疫组织化学方法及逆转录酶链反应检测狼疮肾炎患者和正常对照组外周血单个核细胞NF-κB与糖皮质激素受体mRNA的表达。结果：与对照组相比,狼疮肾炎患者外周血单个核细胞GRmRNA表达水平降低,NF-κB表达水平升高（P〈0．01）;激素治疗前,激素敏感组、激素依赖组及激素抵抗组GRmRNA表达水平均降低（P〈0．01）,NF—κB表达水平升高（P〈0．01）。激素敏感组与激素抵抗组GRmRNA表达水平有统计学差异（P〈0．01）。结论：NF—κB与GRmRNA的异常表达可能与狼疮。肾炎病情及糖皮质激素疗效不同有关。     

1型神经纤维瘤病NF1基因突变检测

目的 检测1例1型神经纤维瘤病(NF1)患者NF1基因的突变.方法 采用PCR和DNA测序法检测1例NF1患者、2例直系亲属及100例无亲缘关系的正常人NF1基因突变.结果 在NF1患儿中检测到1个移码突变c.3822delC,患者直系亲属及100例无亲缘关系的正常对照均未检测到上述突变.结论 在该例NF1患儿中新发现1个NF1基因移码突变c.3822delC不是罕见的单核苷酸多态性,可能是致病突变,通过影响NF1基因的功能致病.     

Local injection of recombinant human stem cell factor promotes human skin mast cell survival and neurofibroma cell proliferation in the transplanted neurofibroma in nude mice

Abstract We studied the effects of stem cell factor (SCF) on human skin mast cell (HSMC) survival and the proliferation of neurofibroma (NF) cells in transplanted NF in nude mice. Small pieces of cutaneous NF from a patient with von Recklinghausen’s disease were transplanted subcutaneously into nude mice. Recombinant human SCF (10 or 100 ng) was injected six or seven times around the NF transplantation sites over 11 days (i.e. every other day). The number of HSMCs was reduced in vehicle-injected NF compared to the amount present before transplantation. In contrast, NF-transplanted animals that were injected with SCF (10 or 100 ng) showed preservation of mast cell numbers in the tissue. Using computerized image analysis, mast cell size in SCF-treated NF transplants was significantly altered (larger at the 10 ng dose, and smaller at the 100 ng dose) compared with the size before transplantation or in vehicle-injected tissue. Furthermore, at the higher SCF dose (100 ng) PCNA-positive NF cells showed a significant increase. These results indicate that HSMCs in transplanted NF tissue retain their capacity to respond to SCF in vivo, and that SCF contributes to the regulation of both HSMC survival and size in cutaneous NF. In addition, activated HSMCs induced by SCF may be involved in the growth of cutaneous NF in von Recklinghausen’s disease. Thus, this experimental model may be useful in the study of the cellular interactions between HSMCs and other stromal cells in cutaneous NF. Received: 9 June 1998 / Received after revision: 30 November 1998 / Accepted: 11 December 1998     

Necrotizing fasciitis: reviewing the causes and treatment strategies

PURPOSE: To update the practitioner with causes, diagnosis, and treatment options for necrotizing fasciitis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in better understanding the pathophysiology, diagnosis, and treatment of necrotizing fasciitis. OBJECTIVES: After reading this article and taking this test, the reader should be able to: 1. Identify the risk factors and causes of necrotizing fasciitis (NF). 2. Describe the clinical presentation and diagnosis of NF. 3. Explain the treatment options for NF.