Cocaïne et lésions destructrices centro-faciales : à propos d'un cas.

INTRODUCTION: Cocaine use is associated with multiple complications, some of which can mimic systemic diseases, especially Antineutrophil Cytoplasmic Antibody (ANCA) associated vasculitis. We report a case of Cocaine Induced Midline Destructive Lesions (CIMDL) for which a diagnosis of granulomatosis with polyangiitis (GPA) was discussed. CASE REPORT: A 42-year-old male, cocaine consumer, was admitted in our department for a centrofacial destructive process. He had no extra ear, nose and throat (ENT) involvement. ANCA were positive with a perinuclear fluorescence pattern and an anti-Proteinase 3 specificity. Regarding this unusual immunologic pattern and in the absence of histological argument for a GPA, a diagnosis of CIMDL was made. CONCLUSION: CIMDL is a centrofacial destructive process due to intranasal cocaine use. It is frequently associated with the presence of p-ANCA with both anti-HNE and anti-PR3 specificity.

Caracterización de lesiones letales de la línea media facial en pacientes del Hospital Escuela Universitario, Honduras entre 2011-2014 / Characterization of lethal injuries of the facial midline in patients of the University School Hospital, Honduras between 2011-2014

Objetivo: Caracterizar lesiones letales de línea media facial, signos y síntomas frecuentes, género y procedencia de los pacientes, histopatología e inmunohistoquímica en base a registros médicos institucionales de HEU entre 2011 y 2014.La lesión letal de línea media es un síndrome que inicialmente engloba variadas entidades: Linfomas no Hogdkin de células NK y T, Linfomas no Hogdkin de células B, enfermedades autoinmunes como la Granulomatosis con Poliangeítis, muchas causas infecciosas e idiopáticas con destrucción acelerada y catastrófica de la región nasofaríngea, senos paranasales y septum nasal. Síndromes de difícil diagnóstico con enfoques terapéuticos muy distintos. Metodología. Se realizó un estudio descriptivo, transversal, con revisión de todos los registros de biopsias realizados en el departamento de Anatomía Patológica del HEU desde el año 2011 al 2014. Cumplen criterios de inclusión, 34 casos. Resultados: Mayor prevalencia de lesiones en hombres 59 %, dentro del rango de edad de 19 a 59 años, con predomino de la región central de Honduras. Signo más frecuente: masa obstructiva. Diagnóstico más consignado fue Linfoma No Hodgkin sin especificación. Conclusión: Frecuencia de lesiones letales de la línea media es mayor en varones, procedentes en su mayoría de región central, síntoma y signo más frecuentes son masa obstructiva con ulceración y la rinorrea purulenta; la utilización de marcadores de inmunohistoquímica es deficiente para definir los casos inespecíficos de Linfoma No Hodgkin Nasales.

Objective: To characterize lethal facial midline lesions, frequent signs and symptoms, gender and origin of the patients, histopathology and immunohistochemistry based on HEU institutional medical records between 2011 and 2014. Lethal midline injury is a syndrome that initially encompasses a variety of entities: non-Hogdkin lymphomas of NK and T cells, non-Hogdkin B-cell lymphomas, autoimmune diseases such as granulomatosis with polyangiitis, many infectious and idiopathic causes with accelerated and catastrophic destruction of the nasopharyngeal region, paranasal sinuses and nasal septum. Syndromes which are difficult to diagnose with very different therapeutic approaches.Methodology. A descriptive, crosssectional study was carried out with a review of all biopsy registries performed in the Department of Pathological Anatomy of HEU from 2011 to 2014. 34 cases meet the inclusion criteria. Results: There was a higher prevalence in men 59%, within the age range of 19 to 59 years, with predominance of the central region of Honduras. Most frequent sign: obstructive mass. Most diagnosed was Non-Hodgkin's lymphoma without specification. Conclusion: Frequency of lethal midline lesions is greater in males, mostly from the central region. The most frequent symptoms and signs are obstructive mass with ulceration and purulent rhinorrhea; the use of immunohistochemical markers is deficient to define nonspecific cases of Nasal Non-Hodgkin's Lymphoma.

Lesões destrutivas da linha média induzidas por cocaína com ANCA positivo mimetizando a granulomatose de Wegener / Cocaine-induced midline destruction lesions with positive ANCA test mimicking Wegener's granulomatosis

O uso crônico de cocaína por inalação pode causar lesões destrutivas de linha média (LDLMIC), que podem ser difíceis de distinguir das lesões da granulomatose de Wegener (GW) nos ouvidos, nariz e garganta. Descrevemos o caso de uma paciente de 43 anos admitida com história de dois anos de obstrução nasal e rinorreia. Ela havia recebido o diagnóstico de GW há cinco meses e estava em tratamento com prednisona e ciclofosfamida. Ao exame físico apresentava perfuração de septo nasal e palato. Exames de laboratório mostraram elevação das proteínas de fase aguda e teste p-ANCA positivo. Ensaios ELISA antiproteinase 3 e mieloperoxidase foram negativos. Tomografia computadorizada (TC) dos seios paranasais mostrou destruição de septo nasal e palato, bem como sinusite maxilar bilateral. TC de tórax resultou normal. Biópsia da mucosa nasal revelou infiltrado inflamatório sem granuloma ou vasculite. Quando questionada, admitiu ser usuária de cocaína há cinco anos. Os imunossupressores foram suspensos e a paciente não mais fez uso da droga. Ela está sendo monitorada há seis meses e não desenvolveu novas lesões ou sintomas de outros órgãos. O diagnóstico diferencial em pacientes com LDLMIC pode ser desafiador. A avaliação deve incluir pesquisa de uso intranasal de cocaína. Embora o teste de ANCA não diferencie claramente o ANCA encontrado em alguns pacientes com LDLMIC daqueles em pacientes com GW, o envolvimento localizado e os achados de biópsia não típicos de vasculite granulomatosa de pequenos vasos devem ser reconhecidos como características das lesões induzidas por cocaína.

Chronic use of cocaine by inhalation may induce midline destructive lesions (CIMDL), which can sometimes be difficult to distinguish from the ear, nose and throat lesions of Wegener's Granulomatosis (WG). We describe the case of a 43-year-old female patient admitted with a two-year history of nasal obstruction and rhinorrhea. She had been diagnosed with WG for five months, being on prednisone and cyclophosphamide. On her physical examination, perforation of her nasal septum and palate was observed. Laboratory tests showed elevated acute phase proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and myeloperoxidase were negative. The paranasal sinus computed tomography (CT) showed destruction of the nasal septum and palate, in addition to bilateral maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned, she admitted being a cocaine user for five years. Medical therapy and cocaine use were withdrawn. She has been followed up for six months and no other lesion or other organ symptoms occurred. Differential diagnosis in patients with midline destructive lesions can be very challenging. Evaluation should include enquiry about intranasal use of cocaine. Although ANCA testing does not clearly differentiate the ANCA found in some patients with CIMDL from those found in WG patients, the localized involvement and the biopsy findings non-characteristic of small vessel granulomatous vasculitis should be recognized as features for cocaine-induced lesions.

Cocaine-induced midline destruction lesions with positive ANCA test mimicking Wegener's granulomatosis.

Chronic use of cocaine by inhalation may induce midline destructive lesions (CIMDL), which can sometimes be difficult to distinguish from the ear, nose and throat lesions of Wegener's Granulomatosis (WG). We describe the case of a 43-year-old female patient admitted with a two-year history of nasal obstruction and rhinorrhea. She had been diagnosed with WG for five months, being on prednisone and cyclophosphamide. On her physical examination, perforation of her nasal septum and palate was observed. Laboratory tests showed elevated acute phase proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and myeloperoxidase were negative. The paranasal sinus computed tomography (CT) showed destruction of the nasal septum and palate, in addition to bilateral maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned, she admitted being a cocaine user for five years. Medical therapy and cocaine use were withdrawn. She has been followed up for six months and no other lesion or other organ symptoms occurred. Differential diagnosis in patients with midline destructive lesions can be very challenging. Evaluation should include enquiry about intranasal use of cocaine. Although ANCA testing does not clearly differentiate the ANCA found in some patients with CIMDL from those found in WG patients, the localized involvement and the biopsy findings non-characteristic of small vessel granulomatous vasculitis should be recognized as features for cocaine-induced lesions.

A peculiar case of midface reconstruction with four free flaps in a cocaine-addicted patient.

SUMMARY: Cocaine-induced lesions may cause extensive destruction of the osteocartilaginous structures of the nose, sinuses and palate, a syndrome called CIMDL (cocaine-induced midline destructive lesion). In such cases, reconstructive procedures of the lost soft and hard tissues may be indicated, such as local flaps, regional flaps, and free revascularised flaps. Also, prosthetic obturators have been suggested to overcome the functional problems related to the tissue loss. However, the majority of publications are related to relatively small defects, whereas articles related to the surgical treatment of large midfacial defects are less frequently reported. The objective of this article is to report the authors' experience concerning a unique case consisting of a complex reconstruction of a severe cranial base, midface, palate, and nose defect following cocaine abuse with four revascularised flaps followed by prosthetic restoration with implant-supported prostheses.

Functional characterization of antineutrophil cytoplasmic antibodies in patients with cocaine-induced midline destructive lesions.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine-induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG). METHODS: PR3 ANCA and NE ANCA were detected by capture enzyme-linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide by NE. RESULTS: IgG from NE ANCA-positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross-inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL. CONCLUSION: The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG.

Extranodal NK/T-cell lymphoma, nasal type.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL), previously known as lethal midline granuloma is a distinct clinico-pathological entity associated with Epstein-Barr virus that typically causes destruction of the midface, palatal and orbital walls. In addition, ENKTCL can involve the skin, soft tissue, testes, gastrointestinal and upper respiratory tract. ENKTCL neoplastic cells express some T-cell associated antigens, most commonly CD2 and cytoplasmic CD3epsilon and, in favour of an NK-cell origin, CD56. Early stage disease may respond to radiotherapy alone, however late stage disease does not respond well to any available therapies. Overall, patients with ENKTCL have a cumulative probability of survival at 5 years ranging from 37.9% to 45.3%.

Bovine nasal eosinophilic, granuloma with blood eosinophilia caused by Nocardia species.

OBJECTIVE: To describe a case of nocardial nasal granuloma in a Holstein heifer. CLINICAL FEATURES: The heifer showed laboured respiration and occasional coughing with granulomatous excrescences on the bilateral nasal mucosa, and a marked leucocytosis with eosinophilia. NECROPSY: Severe granulomatous inflammation with eosinophils, epithelioid cells, giant cells and Nocardia sp obstructed both nasal passages completely. CONCLUSION: This lesion resulted from chronic infection with Nocardia sp and is distinct from other forms of bovine nasal granuloma, also called atopic rhinitis or chronic granular rhinitis, which we propose should be classified as bovine allergic granular rhinitis. The most appropriate name for the present disease is bovine nasal eosinophilic granuloma.

Midfacial granuloma syndrome or an inflammatory non-specific disease? A case report.

We report a case of idiopathic midline destructive disease in a 57-year-old man. The patient had a non-specific histological pattern in biopsies obtained from the nose and upper lip, characterized by a granulomatous reaction with progressive destruction of the tissues. The patient's general medical history was non-contributory. Clinical and laboratory data did not support any feasible etiology for this destructive process. The patient was treated with prednisone until the discovery of type II diabetes mellitus (never diagnosed before) and was then in turn treated only with oral antidiabetic therapy. Follow-up controls revealed progressive reduction of the symptoms and of the nasal and lip lesions and total remission of symptoms up to 2 years after the onset of the disease. We discuss the diagnostic and subsequent therapeutic problems in the management of the midline necrotizing lesions.

Chronological changes in incidences of polymorphic reticulosis in Korea and Japan.

Lethal midline granuloma (LMG) is a clinical term, which describes a group of diseases histologically comprising Wegener's granulomatosis, polymorphic reticulosis (PR), and malignant lymphoma of the ordinary type (ML). PR is a variant of ML, and is considered to be a type of NK/T cell lymphoma. Our previous study revealed the clustering of patients with PR in East Asia including China, Korea and Japan. However, the frequency rate of PR varied even among these countries, with that of Korea being approximately 5 times higher than that of Japan. In the present study, we examined the incidences of each type of LMG, especially PR, in Korea (Yonsei University) and Japan (59 university hospitals) over time. A total of 102 cases and 655 cases of LMG admitted to Yonsei University, Korea from 1977 to 1996 and 59 university hospitals in Japan between 1965 and 1996, respectively, were examined. The frequency rate of PR per 100,000 outpatients of ears, nose and throat (ENT) clinics in Korea decreased from 40 to 20 between the periods of 1977-1989 and 1990-1996. However, there were no significant changes in Japan during the period studied.

Nasal cocaine abuse presenting as a central facial destructive granuloma.

We describe a 36-year-old patient with an aggressive, midline intranasal and naso- and oropharyngeal destructive process. For months the patient denied heavy abuse of nasal cocaine, but finally admitted it. Necrosis and atrophy of the inferior and middle nasal turbinates bilaterally, prominent naso and oropharyngeal ulcers, nasal septal as well as hard palate perforation were observed clinically. Repeated biopsies revealed focal areas of chronic inflammation and necrosis, but there was no evidence of vasculitis or granuloma formation. Since serum was slightly positive for antineutrophil cytoplasmic antibody, the initial diagnosis was Wegener's granulomatosis. In the United States there have been a few reports on a new cocaine-associated syndrome presenting as an aggressive, midline, intranasal and intrapharyngeal destructive process mimicking limited Wegener's granulomatosis and midline reticulosis. We report the first such case in Europe and offer guidelines for the diagnostic work-up of such cases.

Nasal peripheral T-cell lymphoma: a 20-year review of cases treated in Scotland.

The nasal peripheral (post-thymic) T-cell lymphoma is an important cause of the midline granuloma syndrome (MGS), in which ulceration and destruction of the tissues of the nose and paranasal sinuses occurs. We reviewed the histology of 9 cases of the MGS treated with radiotherapy, and, using immunocytochemistry, showed 8 cases to be peripheral T-cell lymphomas (PTCL) and 1 a B-cell lymphoma. All patients received radiotherapy and 2 died shortly after treatment from unrelated causes. Two patients with T-cell lymphoma and the solitary case of B-cell lymphoma achieved long-term disease-free survival. The 4 remaining cases of T-cell lymphoma relapsed locally at a median interval of 3.5 months despite megavoltage irradiation of 45-50 Gy (in 3 cases) and inclusion of uninvolved paranasal sinuses and the nasopharynx in the field (in 2 cases). All patients with local relapse achieved, and remain in, remission after treatment with alkylating agents and prednisolone. The disappointing response of some cases of nasal T-cell lymphoma to radiotherapy has been reported by others, and this may be due partly to the heterogeneity of nasal lymphomas. We are unable to provide clear guidelines for treatment but suggest that a role exists for initial treatment with oral alkylating agents and steroids in newly diagnosed cases.

[Long-term follow-up and therapeutic results of the protocol of the National Society of Internal Medicine in centrofacial malignant granuloma. Report of 40 cases]. / Suivi à long terme et résultats thérapeutiques du protocole de la Société Nationale de Médecine Interne sur les granulomes malins centro-faciaux. A propos de 40 cas.

We have studied 40 cases of mediofacial necrosis with no specific diagnosis on biopsy. After an exhaustive work-up we reached a specific diagnosis in 13 patients (Wegener's granulomatosis in 7, classical malignant lymphoma of the nose in 3, squamous cell carcinoma = "goundou" in 1, syphilis and tuberculosis in 1, aspergillosis in 1). Those patients received the appropriate treatments with good results. The remaining 27 patients, however, had ulcerative lymphomas of the midface (according to the immunofluorescence and molecular biology techniques). Their fate was worse since only 15% remain alive on the long-term, despite intensive treatments with chemotherapy, radiotherapy, interferon, artificial nutrition and antibiotics as needed. We present a new protocol with intensified chemotherapy and growth factor treatment in order to ameliorate the very poor prognosis of these patients.

[Midline granuloma and Wegener's granulomatosis]. / Il "granuloma centro-facciale" e la granulomatosi di Wegener. "Midline granuloma" and Wegener's granulomatosis.

Necrotizing lesions of upper respiratory tract have always been among the most enigmatic diseases of the head and neck region. Nowadays a great deal of nosographic confusion still remains along with numerous doubts concerning diagnostic and therapeutic strategies to be followed in dealing with many diseases often erroneously defined "midline granuloma". In fact, a large variety of diseases appear or may appear as midline destructive lesions in the upper respiratory tract. Each of these, including infections, immune and neoplastic disorders, obviously requires a different therapy. The clinician must have a very good knowledge of the problem in order to make a rational approach to diagnosis and therapy. Wegener's granulomatosis is quite different from "midline granuloma" and must be diagnosed promptly so that an appropriate therapy may be determined as soon as possible. Unlike in the case of "midline granuloma", a prompt therapy is often very effective and gives long periods of remission. In this disease, nevertheless, the etiopathogenesis of both diseases is unknown, precise protocols for diagnosis or treatment do not exist (every case must be considered separately) and prognosis is very poor. On the basis of their personal experience and of an accurate review of Literature, the Authors present a systemic and up-to-date monographic study focusing particular attention on the most recent diagnostic techniques, such as immunohistochemical techniques which utilize monoclonal antibodies, indispensable in the cases of "midline granuloma", and immunofluorescent techniques searching antibodies to cytoplasmic antigens of neutrophil granulocytes, of great value in dealing with Wegener's granulomatosis not only in establishing an initial diagnosis, but also in making prognosis and in controlling the evolution of the disease. The paper also discusses differential diagnosis of midline destructive disorders, highly important for a correct and rational initial approach in diagnosis. Every disease described in the section concerning differential diagnosis must be excluded in order to make an accurate diagnosis of "midline granuloma" in that no typical histopathologic or clinical signs of this particular, destructive disorder. Finally, the authors focus their attention on new etiopathogenetic hypotheses and their therapeutic implications. The most interesting of them are surely those that consider "midline granuloma" the manifestation of a malignant lymphoma as well as those that explain the recent success obtained in treatment of Wegener's granulomatosis using trimethoprim and sulfamethoxazole asserting a possible essential role of infections in the etiology of the disease.