Staging of necrotizing fasciitis based on the evolving cutaneous features

BACKGROUND: Necrotizing fasciitis is a severe soft-tissue infection characterized by a fulminant course and high mortality. Early recognition is difficult as the disease is often clinically indistinguishable from cellulitis and other soft-tissue infections early in its evolution. Our aim was to study the manifestations of the cutaneous signs of necrotizing fasciitis as the disease evolves. METHODS: This was a retrospective study on patients with necrotizing fasciitis at a single institution. Their charts were reviewed to document the daily cutaneous changes from the time of presentation (day 0) through to day 4 from presentation. RESULTS: Twenty-two patients were identified. At initial assessment (day 0), almost all patients presented with erythema, tenderness, warm skin, and swelling. Blistering occurred in 41% of patients at presentation whereas late signs such as skin crepitus, necrosis, and anesthesia were infrequently seen (0-5%). As time elapsed, more patients had blistering (77% had blisters at day 4) and eventually the late signs of necrotizing fasciitis characterized by skin crepitus, necrosis, and anesthesia (9-36%) were seen. A clinical staging system was developed based on our observations. Stage migration from early to late stage necrotizing fasciitis was evident with majority of patients in stage 1 at day 0 (59%), whereas by day 4, majority had developed into stage 3 (68%). CONCLUSION: This study has demonstrated the continuum of cutaneous manifestations as necrotizing fasciitis evolves. This will help in the early recognition and intervention of this devastating condition.     

Vibrio vulnificus infection. Case report and update since 1970

Vibrio vulnificus infections is being reported with increasing frequency in coastal regions of the United States. Raw seafood consumption, particularly raw oysters, and wounds acquired in a marine environment predispose to infection. Patients with advanced liver disease are at increased risk of developing septicemia. V. vulnificus is a virulent pathogen producing significant morbidity and mortality; its virulence relates in part to the production of exotoxin. Skin lesions occur early in the clinical course of infection and provide means of specific diagnosis. The patient and the consulting physician are well served by the dermatologist capable of recognizing this infectious disease.     

Necrotizing dermatitis due to Vibrio Vulnificus]

BACKGROUND: Vibrio vulnificus is a Gram-negative halophilic pathogen for man that can cause septicemia in patients with chronic liver disease. In healthy subjects, infections are generally local or regional. We report two cases of necrotizing dermo-hypodermitis due to Vibrio vulnificus. CASE REPORTS: The first patient was a 21-year-old fisherman who developed extensive necrotizing dermo-hypodermitis 24 hours after a penetrating scratch with a fish bone. The second patient was also a fisherman. This 35-year-old man developed a massive area of necrotic tissue on the left leg, also 48 hours after a penetrating fish bone scratch. Both patients exhibited neutrophil hyperleukocytosis and thrombocytopenia. Bacteriological study of the pus and damaged tissue identified Vibrio vulnificus. Blood cultures were negative. Liver tests and liver ultrasound were normal. The course was favorable in both cases with antibiotic treatment and excision of the necrotic tissue. DISCUSSION: For these two cases of Vibrio vulnificus necrotizing dermo-hypodermitis, the diagnosis was based on epidemiological, clinical and bacteriological arguments. Neither of these patients had liver disease, explaining the limited locoregional nature of the infection. The severity of the skin necrosis and its rapid course are related to the toxins produced by V. vulnificus. Curative medical and surgical care is generally effective in cases without septicemia and prognosis is good. Education of exposed subjects, fishermen and patients with chronic liver disease, should be helpful for prevention.     

Vibrio vulnificus septicemia in Korea: clinical and epidemiologic findings in seventy patients

We studied the clinical characteristics and the epidemiology of primary septicemia associated with Vibrio vulnificus in 70 patients. All patients came from the western and southern coastal areas of Korea. Most cases (96%) occurred during the summer months, in men (96%), and in persons 40 or more years of age (90%). The illness of 46 patients (66%) began with septicemia, often within 2 days of the consumption of raw seafood. Forty-seven patients (67%) had preexisting hepatic disease, and 49 (70%) had a history of alcoholism. Of the 70 patients, 45 (79%) died. The cutaneous lesions that were present on admission in 64 patients (91%) appeared on the legs in 51 of the cases. V. vulnificus was isolated from the blood of 65 patients tested and from the skin lesions of 51 of 55 patients tested. The histopathologic findings differed according to the clinical stage of lesions. Because V. vulnificus septicemia is a highly fatal disease, persons with liver disease or alcoholism should avoid eating or handling raw seafood.     

Infections with Vibrio vulnificus

V. vulnificus is an uncommon cause of soft tissue infection and primary septicemia, especially in patients with hepatic disease or who patients who are immunocompromised. The mortality of infection in these patients is extremely high despite timely antibiotic therapy. It is important to consider the possibility of infection with V. vulnificus in patients who present with high fever and rapidly progressive sepsis and have a history of consumption of raw seafood (especially oysters) or exposure of open wounds in a marine environment. Public education regarding the risk of raw seafood consumption is essential to preventing infection with this virulent pathogen.     

OYSTERS, IRON OVERLOAD AND VIBRIO VULNIFICUS SEPTICAEMIA

A case of Vibrio vulnificus septicaemia complicated by cutaneous leg ulceration is described. A 74 year old man with haemochromatosis and sideroblastic anaemia developed an acute febrile illness with cutaneous manifestations 24 hours after ingesting raw oysters. The presence of blistering should be considered an important clue to the diagnosis of Vibrio vulnificus septicaemia, and this can facilitate prompt effective antimicrobial therapy. Clinicians should be aware of this infection because of its high case fatality rate, especially in patients with iron overload states.     

Skin microflora and bacterial infections of the skin

The skin is a milieu for controlled bacterial growth. Skin supports the growth of commensal bacteria, which protect the host from pathogenic bacteria. Environmental and local factors, host immunity, and organism adherence and virulence are intricately related to cutaneous infection. Resident gram-positive bacteria include Staphylococcus, Micrococcus, and Corynebacterium sp. Staphylococcus aureus and Streptococcus pyogenes are notoriously pathogenic in the skin. In order for bacteria to be pathogenic, they must be able to adhere to, grow on, and invade the host. Bacteria possess numerous virulence genes that allow for growth in these privileged niches. Epidermal infections caused by S. aureus and S. pyogenes include impetigo and ecthyma. Dermal infections consist of erysipelas, cellulitis, and necrotizing fasciitis. The pilosebaceous unit is involved in folliculitis, furunculosis, and carbunculosis. Moreover, S. aureus and S. pyogenes produce toxins that may elicit a superantigen response, causing massive release of cytokines. Staphylococcal scalded skin syndrome, toxic shock syndrome, and scarlet fever are all superantigen-mediated. Gram-negative organisms such as Pseudomonas aeruginosa, Pasteurella multocida, Capnocytophaga canimorsus, Bartonella sp., Klebsiella rhinoscleromatis, and Vibrio vulnificus are not typical resident skin microflora but may cause cutaneous infection.     

Vibrio vulnificus infection and metalloprotease

Vibrio vulnificus is ubiquitous in aquatic environments; however, it occasionally causes serious and often fatal infections in humans. These include invasive septicemia contracted through consumption of raw seafood, as well as wound infections acquired through contact with brackish or marine waters. In most cases of septicemia, the patients have underlying disease(s), such as liver dysfunction or alcoholic cirrhosis, and the secondary skin lesions including cellulitis, edema and hemorrhagic bulla appear on the limbs. Although V. Vul produces various virulent factors including polysaccharide capsule, type IV pili, hemolysin and proteolytic enzymes, the 45-kDa metalloprotease may be a causative factor of the skin lesions, because the purified protease enhances vascular permeability through generation of chemical mediators and also induces serious hemorrhagic damage through digestion of the vascular basement membrane. As well as other bacteria, V. Vul can regulate the protease production through the quorum-sensing system depending on bacterial cell density. However, this system operates efficiently at 25 degrees C, but not at 37 degrees C. Therefore, V. vulnificus may produce sufficient amounts of the protease only in the interstitial tissue of the limbs, in which temperature is lower than the internal temperature of the human body.     

Early detection of streptococcal group antigens in skin samples by latex particle agglutination

The streptococcal group antigens (A to G) were researched in skin biopsy specimens by a latex agglutination technique using commercial (Slidex Streptokit bio-Mérieux and Streptex Wellcome) and experimental reagents. Twenty-seven patients with obvious cutaneous infections (12 cases of erysipelas, nine cases of cellulitis, and six cases of necrotizing fasciitis) and 27 age- and sex-matched controls were studied. Our preliminary data demonstrated the possibility of an early diagnosis of streptococcal cutaneous infections involving the deep dermis and/or hypodermis. We used a latex agglutination technique that is quite specific and gives a better sensitivity (0.63) than either conventional bacteriologic cultures on needle aspiration or skin biopsy specimens.     

Epidemiological survey of Vibrio vulnificus infection in Japan between 1999 and 2003

The frequency of Vibrio vulnificus infection is very rare and there are many questions regarding its epidemiology in Japan. To investigate the clinical course and epidemiology of V. vulnificus infection in Japan, we performed a retrospective questionnaire survey in which 1693 hospitals from all over Japan were surveyed, including advanced life saving emergency centers and dermatology institutions. Of the 1693 hospitals, we received answers from 1045. Ninety-four cases were confirmed as V. vulnificus infections during 1999 and 2003. Sixty-eight (72.3%) of the 94 patients had the septic type infection with a mortality rate of 75.0% (51/68 patients died). The prognosis of patients with the septic type was worse than that of the wound type (P < 0.001). V. vulnificus infections occurred from June to November and none occurred in winter. Many infections occurred in western Japan with the majority of infections (50/94) occurring in Kyushu. In particular, 43 infections occurred in marine coastal areas of the Ariake and Yatsushiro Seas, which have many tidelands. Seventy-seven of 89 patients (86.5%) had liver function impairment as an underlying disease, and 53 (59.6%) had liver cirrhosis, of whom nine (10.1%) suffered from liver cancer. The incidence of V. vulnificus infection was different according to districts. Geographic and climatic factors also contributed to the occurrence of V. vulnificus infection.     

Skin changes in drug-dependent patients

In parenteral drug abuse, cutaneous manifestations are very common. A variety of skin lesions are indicators of a possible drug addiction: obliteration of peripheral veins and hyperpigmentation of the overlying skin, punched-out scars due to subcutaneous injection, persistent edema following thrombophlebitis, and excoriations due to heroin pruritus. Infectious and non-infectious complications may be accompanied by typical skin alterations, such as ecthyma in sepsis caused by Pseudomonas aeruginosa, multiple ulcers due to embolic infarct, or hypersensitivity reactions mediated by an immunological process. A variety of serious complications may develop at the injection sites: abscesses, gangrene, necrosis, or necrotizing fasciitis. These examples show that the dermatologist is in many ways involved in the care for addicted patients. In addition, these patients frequently suffer from sexually transmitted diseases or blood-borne infections; HIV-infection is rapidly spreading in this group. We now face new problems of differential diagnosis, especially since constitutional symptoms of HIV-infection may mimic symptoms of drug abuse and vice versa. Moreover, immunological alterations similar to those in HIV patients may even occur in drug addicts who are not infected with the virus.     

Fulminant group A streptococcal necrotizing fasciitis: clinical and pathologic findings in 7 patients

BACKGROUND: Necrotizing fasciitis is a rapidly progressive soft tissue infection with high morbidity and mortality rates. Examination of deep incisional biopsy specimens can provide prompt diagnosis and improve survival. We describe 7 patients with necrotizing fasciitis caused by group A Streptococcus species. OBJECTIVE: Our purpose was to describe the unique dermatopathology and clinical features in 7 patients with necrotizing fasciitis caused by group A Streptococcus. METHODS: We conducted a retrospective review. RESULTS: The average age of the patients was 47 years. Fasciitis occurred on an extremity in all cases. All 5 patients with streptococcal toxic shock syndrome died of their disease. The histopathologic findings from early fascial disease revealed superficial epidermal necrosis, edema, and hemorrhage with few inflammatory cells, whereas clinically advanced, necrotic skin lesions revealed diffuse necrosis, thrombosis, neutrophilia, and numerous gram-positive diplococci. CONCLUSIONS: Patients with clinical features of necrotizing fasciitis should have a deep incisional biopsy specimen obtained from the central area of ecchymotic, necrotic plaques to confirm the diagnosis. Immediate surgical intervention is necessary to reduce the morbidity and mortality rates associated with necrotizing fasciitis.     

Diabetes mellitus

Dermatologic problems are common in diabetes, with approximately 30% of patients experiencing some cutaneous involvement during the course of their illness. Skin manifestations generally appear during the course of the disease in patients known to have diabetes, but they may also be the first presenting sign of diabetes or even precede the diagnosis by many years. The skin involvement can be autoimmune in nature, such as acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma annulare, or infectious in the form of erythrasma, necrotizing fasciitis, and mucormycosis. Pharmacologic management of diabetes, in addition, can also result in skin changes, such as lipoatrophy and lipohypertrophy, at the site of injection of insulin, and oral antidiabetic agents can cause multiple skin reactions as adverse effects. The management of these cutaneous manifestations is tailored according to the underlying pathophysiology, but a tight control of blood glucose is a prerequisite in all management strategies.     

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.     

A fatal case of pancreatic panniculitis presenting in a young patient with systemic lupus

BACKGROUND: Subcutaneous fat necrosis associated with pancreatic disease is a rare event. The clinical cutaneous findings are non-specific erythematous nodules with central softening located predominantly on the lower extremities. The histopathologic features of these lesions are very characteristic and diagnostic. METHODS: We present an unusual case of pancreatic panniculitis associated with lupus pancreatitis in a 21-year-old African American female. The patient presented with lower extremity skin nodules, arthralgia, and serositis prior to the diagnosis of systemic lupus and pancreatitis. The skin lesions progressed despite normalization of serum pancreatic enzymes. Following femoral vein catheterization for renal dialysis, she developed a large indurated area over the left lower quadrant, flank, groin, and upper thigh measuring 25 cm. She was treated with repeated debridement, tissue grafts, and hyperbaric oxygen because of a clinical suspicion of necrotizing fasciitis. RESULTS: Examination of skin biopsies and debrided tissue revealed the pathognomonic features of pancreatic panniculitis without any evidence of necrotizing fasciitis. Organisms were not detected by tissue examination or microbiologic cultures. CONCLUSIONS: This case illustrates the potential role of vascular trauma in the pathogenesis of pancreatic panniculitis.     

Necrotizing Fasciitis in Association with Hyperimmunoglobulin E Syndrome

A case of necrotizing fasciitis in association with hyperimmunoglobulin E (HIE) syndrome is reported. The patient was a 17-year-old Japanese boy with a clinical history of recurrent skin and pulmonary infections and eczematoid dermatitis, markedly elevated serum levels of IgE, and coarse facies. He had a gangrenous swelling on the lower abdominal wall, and his general condition was poor with high fever. The involved site was accompanied by subcutaneous gas; the culture of the pus of the lesion grew anaerobes without mixed growth of Staphylococcus aureus. Exhaustive debridment of necrotic fascia, which extended much farther than the gangrenous area, and administration of antibiotics had a curative effect on the gangrenous soft tissue infection. To the best of the authors' knowledge, this is the first published case of necrotizing fasciitis in association with HIE syndrome.     

Skin diseases in Turkish renal transplant recipients

BACKGROUND: Organ transplant recipients are predisposed to a variety of cutaneous complications due to immunosuppressive therapy. We aimed to determine the prevalence and the clinical spectrum of skin diseases in renal transplant recipients (RTRs). METHODS: One hundred and eleven RTRs were examined at the Renal Transplantation Center in Ege University Hospital between October 1999 and October 2001. The effects of age, gender and duration time after transplantation on cutaneous manifestations were evaluated and the dermatologic manifestations in RTRs were compared with findings in a control group consisting of 100 patients. The t-test, chi2 test and Fisher's exact test were used for statistical analysis. RESULTS: Seventy-five patients (66.4%) had an infection of the skin, 66 patients (58.4%) had drug-related manifestations, and 11 patients (9.7%) had premalignant or malignant skin lesions. Human papilloma virus (HPV) infections were the most common skin lesions. There was no significant relation between age and gender and the incidence of skin diseases in RTRs. The incidence of HPV infections, tinea versicolor and premalignant and malignant lesions increased with the duration of immunosuppression. The incidence of infectious skin diseases, especially HPV infections and tinea versicolor, was higher in the study group than in the control group. CONCLUSIONS: In this study, we observed that cutaneous lesions, especially those caused by infectious diseases, had a higher frequency in RTRs. The findings emphasize the importance of regular dermatological screening in these patients, which can provide early diagnosis and a better quality of life for RTRs.     

Skin manifestations in patients with HIV infection

Cutaneous manifestations are common in patients with HIV infection and mainly due to the immunodeficiency. In the initial stage of HIV infection, we frequently observe a rash of macular lesions. During the asymptomatic phase, the patients may typically show the following skin diseases: seborrhoic dermatitis, acneiform folliculitis, persistent herpes simplex, and infections with the human papilloma virus. In ARC and AIDS patients, 3 groups of skin disorders are found: cutaneous infections, skin tumors, and other mixed skin diseases. Herpes simplex and herpes zoster may develop into ulcerating and necrotising forms especially in patients with advanced immunodeficiency. The most frequent skin tumors in AIDS patients are the disseminated Kaposi's sarcoma and non-Hodgkin's lymphoma. More than 50% of the AIDS patients treated with trimethoprim/sulfamethoxazole developed a severe drug eruption. African and Caribbean patients with AIDS frequently suffer from pruritic skin lesions, the pathogenesis of which is not known. Aside from these cutaneous manifestations, a variety of other skin disorders have been reported in patients with HIV infection, ARC, or AIDS; future research will furnish definite proof whether they are correlated with HIV infection.     

Palisading neutrophilic granulomatous dermatitis in a Japanese patient with Wegener's granulomatosis

Wegener's granulomatosis (WG) is an etiologically obscure entity with multiple systemic manifestations. Recently, cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) has become recognized as a valuable adjunct in the diagnosis of this disorder. WG typically involves the upper airway, lungs, and kidneys, but any other organ can be involved, including the skin. We encountered a unique case in which a 27-year-old Japanese man with WG presented with various typical cutaneous manifestations. Purpuric skin lesions and erythematous rash on the lower extremities progressively involved and changed into a necrotizing ulceration on his toe. Additionally, several nodules developed on the extensor surfaces of his elbows. His serum C-ANCA level increased remarkably. Leukocytoclastic vasculitis, the most common histopathological finding in WG patients, was detected in a purpuric lesion on his hand. A biopsy of a nodule on his elbow revealed palisading epithelioid histiocyte granulomas with features of leukocytoclastic vasculitis. The distinctive pattern of papules has been referred to as "palisading neutrophilic granulomatous dermatitis". An open lung biopsy confirmed WG with focal necrotizing granuloma. A renal biopsy demonstrated necrotizing vasculitis and crescentic glomerulonephritis. He showed a good response to oral corticosteroids and cyclophospamide with total remission of symptoms. We believe that a careful balance between the clinical manifestations and the histopathological evidence allows for timely treatment of WG, which may prevent serious morbidity or death. Although uncommon, WG can present with various types of accompanying cutaneous lesions. Therefore, clinicians should keep this diagnosis in mind when presented with these manifestations.