Clinicopathologic analysis of atypical hand, foot, and mouth disease in adult patients.

BACKGROUND: Hand, foot, and mouth disease is a contagious viral infection usually affecting children. A resurgence of cases in adults, mainly caused by coxsackievirus A6 and with an atypical and more severe presentation, has taken place. OBJECTIVE: The goal was to examine the clinical, histologic, and immunohistochemical features of this disease in adults. METHODS: This is a retrospective study on documented cases of adult hand, foot, and mouth disease from France's Dermatology Department of Strasbourg University Hospital and Bel-Air Hospital in Thionville. RESULTS: Six patients with severe and atypical presentation were included, 4 caused by coxsackievirus A6. The histologic features were: spongiosis, neutrophilic exocytosis, massive keratinocyte necrosis, shadow cells in the upper epidermis, vacuolization of basal cells, necrotic cells in follicles and sweat glands, dense superficial dermal infiltrate of CD3+ lymphocytes, and strong granulysin expression. LIMITATIONS: This is a retrospective case series. CONCLUSION: In adult patients presenting with atypical hand, foot, and mouth disease caused by coxsackievirus A6, biopsy specimens show distinctive changes in the epidermis but also in adnexal structures. The inflammatory infiltrate is made of T cells with a cytotoxic profile, with numerous granulysin-positive cells, as observed in severe drug-induced eruption with necrosis of keratinocytes.

Histopathological study of six types of adverse cutaneous drug reactions using granulysin expression.

BACKGROUND: Few studies have been published on the histopathology of cutaneous adverse drug reactions (CADR), and most of these lack information on skin allergological tests. The histopathology of drug reaction with eosinophilia and systemic symptoms (DRESS) is also seldom described. The purpose of our study was to examine six types of well-documented CADR (maculopapular exanthema, DRESS, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis [TEN], and acute generalized exanthematous pustulosis) using histopathology and immunohistochemistry to evaluate the expression of granulysin, a key molecule in TEN. METHODS: We retrospectively included 106 skin biopsies performed in proven cases of CADR (by chronological investigation, single attributable drug, or/and skin tests). All slides were reviewed, and microscopic changes were analyzed using a standardized form. Granulysin expression was studied by immunohistochemistry. RESULTS: In DRESS, we observed spongiosis, edema, and basal vacuolization, with rare necrotic keratinocytes and constant lymphocytic infiltrate in the superficial dermis. Eosinophils were often present, and pustules were found in 15% of cases. Necrotic keratinocytes are often absent in maculopapular exanthema. Granulysin was expressed in six types of CADR with a trend toward more intense expression in DRESS and TEN. CONCLUSION: We detailed further about the histopathology of DRESS. Granulysin expression was observed in all CADR with a marked overlap of expression pattern between the six types.

Brain endothelial TAK1 and NEMO safeguard the neurovascular unit.

Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP). This leads to severe neurological symptoms, but the mechanisms underlying brain involvement were unclear. Here, we show that selectively deleting Nemo or the upstream kinase Tak1 in brain endothelial cells resulted in death of endothelial cells, a rarefaction of brain microvessels, cerebral hypoperfusion, a disrupted blood-brain barrier (BBB), and epileptic seizures. TAK1 and NEMO protected the BBB by activating the transcription factor NF-κB and stabilizing the tight junction protein occludin. They also prevented brain endothelial cell death in a NF-κB-independent manner by reducing oxidative damage. Our data identify crucial functions of inflammatory TAK1-NEMO signaling in protecting the brain endothelium and maintaining normal brain function, thus explaining the neurological symptoms associated with IP.

Clinical impact of negative-pressure wound therapy: a 1,126-patient observational prospective study.

Negative-pressure wound therapy (NPWT) was developed in the early 1990s and reported in 1997 by Argenta and Morykwas. Ignored at first, this technique progressively came to be considered as an outstanding advancement in reconstructive surgery. Several randomized controlled studies produced evidence for the effect of NPWT on promotion of granulation tissue formation and prevention of tissue damage and amputation. However, no important longitudinal study has yet produced clinical and economic data on the consequences of integrating NPWT into practice in multiple institutions. This prospective, comparative longitudinal study of NPWT as a clinical-practice innovation was conducted in 1,126 patients between March 2006 and June 2009 in 30 university and nonuniversity public and private hospitals in France. NPWT was proposed in a nonrandomized fashion for various clinical indications, and the patients were divided into two groups, one using NPWT, the second using standard care. Efficacy criteria were spontaneous closure, closure after surgical coverage using skin grafts or flaps, or achievement of 40% wound area regression. The results, observed in a pragmatic but not randomized study, are suggestive of a favorable impact of NPWT in multiple clinical situations. The significance of differences between surgical patients who underwent NPWT and those who did not was unclear, as NPWT had already been adopted by most of the surgical wards.

Distinctive features of melanoma and its management in elderly patients: a population-based study in France.

IMPORTANCE: Life expectancy is increasing in most developed countries, and elderly people have the highest incidence of melanoma. OBJECTIVE: To identify characteristics of melanoma and its management in the elderly compared with younger patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective population-based study of incident cases of primary melanoma in 1621 patients with stage I or II melanoma in 2004 and 2008. Questionnaires administered to physicians and a survey of cancer registries and pathology laboratories were used to obtain data. The study was conducted in 5 regions in northeastern France. MAIN OUTCOMES AND MEASURES: Characteristics of patients and tumors, circumstances of diagnosis, and further management in older patients (≥70 years, 487 patients [30.0%]) compared with younger ones (<70 years, 1134 [70.0%]). RESULTS: Older patients had more frequent melanomas of the head and neck (29.4% vs 8.7%; P < .001) and of the nodular, lentigo maligna, or acral lentiginous histologic subtypes. They had thicker and more frequently ulcerated tumors, categorized as T3 or T4 in 36.7% of cases vs 20.1% in younger patients. Diagnosis of melanoma occurred more frequently in a general practice setting and less frequently in direct consultation with a dermatologist or regular screening for skin cancer. Time to definitive excision was longer in older patients, and 16.8% of them compared with 5.0% of the younger population had insufficient excision margins (P < .001). A sentinel lymph node biopsy was performed in 23.3% of the older patients with melanoma thicker than 1 mm vs 41.4% in the younger patients (P < .001). Adjuvant therapy was less frequently started in older patients and was prematurely stopped in a higher proportion of that population. CONCLUSIONS AND RELEVANCE: Age-related variations are observed at every step of melanoma management. The most important concerns are access of elderly people to settings for early diagnosis and excision with appropriate margins.

Clinical and sociodemographic characteristics associated with thick melanomas. A population-based, case-case study in France.

OBJECTIVE: To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, 3 mm) in France. DESIGN: Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING: Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES: Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comte', and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES: Circumstances of diagnosis,clinical and pathological characteristics of melanomas,and sociodemographic characteristics of patients(age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS: Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas.The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis,factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated,divorced, or widowed. When only factors related to patients were taken into account, older age, male sex,and living alone were independent risk factors for VTM.The most significant risk was observed for patients living alone. CONCLUSIONS: Intrinsic factors related to the tumor and socio demographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs.

The role of circumstances of diagnosis and access to dermatological care in early diagnosis of cutaneous melanoma: a population-based study in France.

OBJECTIVES: To describe circumstances of the diagnosis and access to dermatological care for patients with cutaneous melanoma (CM) and to investigate factors associated with early detection. DESIGN: Retrospective population-based study of incident cases of invasive CM in 2004, using questionnaires to physicians and a survey of cancer registries and pathology laboratories. SETTING: Five regions in northeastern France. PATIENTS: Six hundred fifty-two patients who were referred to dermatologists by general practitioners (group 1) or by other specialists (group 2), who directly consulted a dermatologist for CM (group 3), or who were diagnosed as having CM during a prospective follow-up of nevi (group 4) or when consulting a dermatologist for other diseases (group 5). MAIN OUTCOME MEASURES: Characteristics of patients, tumors, and patients' residence in each group, including the geographical concentration of dermatologists. We performed multivariate analysis of these factors to determine association with Breslow thickness. RESULTS: Age, tumor location, Breslow thickness, ulceration, histological type, and geographical concentration of dermatologists significantly differed among groups. Patients consulting dermatologists directly formed the largest group (45.1%). Those referred by general practitioners (26.1%) were the oldest and had the highest frequency of thick (>3 mm), nodular, and/or ulcerated CM. Patients from groups 4 (8.4%) and 5 (14.1%) had the thinnest CMs. Ulcerated and/or thick tumors were absent in group 4. In multivariate analysis, histological types superficial spreading melanoma and lentigo maligna melanoma, younger age, high concentration of dermatologists, and detection by dermatologists were significantly associated with thinner CMs. CONCLUSION: Easy access of patients to dermatologists, information campaigns targeting elderly people, and education of general practitioners are complementary approaches to improving early detection.

Variations in management of stage I to stage III cutaneous melanoma: a population-based study of clinical practices in France.

OBJECTIVE: To describe current management of cutaneous melanoma (CM) and identify factors accounting for disparities. DESIGN: Retrospective population-based study using survey of cancer registries and pathology laboratories, and questionnaires to physicians. SETTING: Five regions covering 19.2% of the French territory and including 8.2 million inhabitants. PATIENTS: Incident cases of patients with stage I to stage II (hereinafter, stage I-II) tumors staged according to the American Joint Committee on Cancer Staging guidelines and nodal stage III CM in 2004. MAIN OUTCOME MEASURES: Modalities of diagnosis and excision, surgical margins, sentinel lymph node biopsy, adjuvant therapies and surveillance procedures, and their variations according to age, sex, residence, location of primary CM, Breslow thickness, type of physicians, modalities of decisions, and health care patterns. RESULTS: Clinical stage I-II CMs (n = 710 cases) slightly predominated in females (53%), with a lower mean Breslow thickness (1.4 mm) than in males (1.9 mm). Initial excisions were most often performed by private dermatologists and wide excisions by surgeons. Narrow margins (8%) were associated with advanced age, higher Breslow thickness, and head location. Sentinel lymph node biopsy was performed in 34% of CMs thicker than 1.0 mm, depending on geographical regions, distance from reference centers, and health care patterns. Adjuvant therapies (mainly low-dose interferon) were proposed in 53% of thick CMs (>1.5 mm), depending on the patient's age and geographical region. In contrast with French recommendations, surveillance procedures frequently included systematic medical imaging. Stage III nodal CMs (n = 89 cases) predominated in males (62%). After lymphadenectomy, adjuvant therapies (including high-dose interferon in 32% of cases and chemotherapies in 24% of cases) were proposed in 68% of cases, depending on the patient's age and geographical region. A complete 1-year high-dose interferon regimen was administered in less than 10% of cases. CONCLUSION: Large disparities still exist in the management of CM in France, depending to a greater extent on medical and geographical environment than on the characteristics of either patients or tumors.

[Cutaneous and osteoarticular Scedosporium apiospermum infection]. / Infection cutanée et ostéoarticulaire à Scedosporium apiospermum.

Scedosporium apiospermum is a widely distributed fungus that can be found in the soil, manure and decaying vegetation. Human infection with this fungus is facilited by immunodepression. A 65-year-old man, who was taking oral methylprednisolone for rheumatoid polyarthritis had for a few months ulcerated or suppurative nodules whose incision discharged a thick honey-colored exudate. An ulceration over the first right metatarsophalangian articulation had left the bone exposed. The treatment for Pseudomonas aeruginosa, initially isolated in the exudate was unsuccessful. Other microbiology samples exhibited Scedosporium apiospermum, without bacteria. The pathogenic nature of the infection was proven on a skin and bone (head of the first metatarsian) biopsy showing numerous branching and septate hyphae. The patient was successfully treated by itraconazole. Scedosporium apiospermum is the cause of a growing number of human infections due to widespread use of immunosuppressors. Skin and lung localizations predominate. Osteoarticular infection is relatively rare, which contributes to the originality of this observation. Treatment is not well defined and essentially combines surgical drainage with antifungals like itraconazole. This emergent fungal infection, which has non specific clinical manifestations, must be considered in immunocompromised patients.