Study on the status quo and correlation between body image and stigma of drug-resistant tuberculosis patients treated with Clofazimine / 中国实用护理杂志

Objective:To investigate the current situation of body image and stigma of drug-resistant tuberculosis patients treated with Clofazimine, and analyze the correlation between them.Methods:A cross-sectional study was conducted using convenience sampling method to investigate 150 patients with drug-resistant tuberculosis treated with Clofazimine in tuberculosis ward of Chengdu Public Health Clinical Medical Center from October 2020 to October 2021. The general questionnaire, Body Image Scale (BIS) and Tuberculosis Related Stigma Scale were used to conduct a questionnaire survey.Results:A total of 130 questionnaires were effectively collected. The body image score of 130 patients with drug-resistant tuberculosis treated with Clofazimine was (20.51 ± 6.80) points; the score of stigma was (17.78 ± 6.92) points. There was a positive correlation between the total score of disease shame and the total score of body image ( r=0.544, P<0.05). Conclusions:Patients with drug-resistant tuberculosis treated with Clofazimine have body image disorder and stigma, and the two are positively correlated. Caregivers should carry out psychological assessment and intervention at an early stage to improve the patient′s mental health level.

Adverse effects of polychemotherapy for leprosy in 13 years of follow-up at a university hospital

Abstract Leprosy is one of the neglected diseases in the world and Brazil is the second country with more cases. A retrospective study was conducted based on the medical records of 196 leprosy patients diagnosed during the course of 13 years at a university hospital. The aim was to describe the adverse effects of polychemotherapy, as well the most prevalent and most vulnerable populations. In the study, dapsone was the most implicated drug, especially in women, and the risk increased with age. The authors conclude that with this patient profile, greater vigilance should be taken regarding possible adverse effects, especially anemia.

Ultra-short-course and intermittent TB47-containing oral regimens produce stable cure against Buruli ulcer in a murine model and prevent the emergence of resistance for

Buruli ulcer (BU), caused by

Information on Drugs Used in Management of Lepra Reactions in Commonly used Drug Information Sources in India

Availability of adequate and proper drug information helps in rational prescription of essential drugs. This can be obtained from various sources such as National Formularies; other sources such as Current Index of Medical Specialties, Monthly index of medical specialties and the information available with the regulators and drug package inserts (PI). In this study, we assessed the drug information of the drugs used for treatment of both type of lepra reactions. Five drugs used for treating Lepra reactions were analyzed for any variation (Qualitative) in information on various parameters as mentioned in commonly used drug information sources such as CIMS India, MIMS India, Central Drugs and Standards Control Organization (CDSCO) website and National Formulary of India (NFI). We observed some gross qualitative variation regarding drug information given in different commonly used sources. Variation exists in the quality of information available on indications, contraindications, dosage and completeness of the dosing schedule about drugs available in various sources. As management of Lepra reactions is crucial in achievement desirable outcome of treatment of leprosy, it is important that information regarding drugs used for such indications should be 100% uniform in all commonly used and available sources.

Ashy dermatosis with involvement of mucous membranes

Abstract: Ashy dermatosis is a rare condition, of unknown aetiology, in which mucous membranes are typically spared. The authors report the case of a 57-year-old female with a history of asymptomatic gray-bluish macules located on the trunk and oral mucosa. There were no relief changes on examination. Skin biopsies from the oral mucosa and trunk were performed and both were compatible with ashy dermatosis. The patient started treatment with oral clofazimine but due to the absence of clinical improvement the drug was discontinued three months later. This case report illustrates an atypical case of ashy dermatosis owing to the involvement of mucous membranes, which is rarely described in the literature.

Dermatosis cenicienta / ashy dermatosis

La dermatosis cenicienta es una hipermelanosis idiopática con máculas de color azul grisáceo, que fue descrita inicialmente en El Salvador por Oswaldo Ramírez en 1957. Predomina en la población hispana de piel fototipo IV, siendo más común en adultos entre la segunda y tercera década de la vida. Aunque se desconoce la etiología, se han identificado factores predisponentes como la ingesta de nitrato de amonio, benzodiacepinas, exposición a pesticidas y fungicidas como clorotalonil, entre otros. A nivel histopatológico se visualiza degeneración e hiperpigmentación de la capa basal. Clínicamente, el tórax y las extremidades proximales son las áreas anatómicas comúnmente afectadas en esta enfermedad asintomática y de curso crónico. La historia clínica y el examen físico son la base del diagnóstico, así como una biopsia de piel de los bordes activos para confirmar el mismo. Aunque existen diversas opciones terapéuticas, solamente la clofazimina y la dapsona han mostrado eficacia en el tratamiento de la dermatosis cenicienta. El líquen plano pigmentado y la pigmentación macular eruptiva idiopática son dos de los principales diagnósticos diferenciales que el clínico debe considerar.

Ashy dermatoses is an idiopathic hypermelanosis with blue-gray macules, which was first described by Oswaldo Ramírez in El Salvador in 1957. It predominates in the Hispanic population with skin type IV, being most common in adults between the second and third decade of life. Although the etiology is unknown, predisposing factors have been identified as the intake of ammonium nitrate, benzodiazepines, exposure to pesticides and fungicides such as chlorothalonil, etc. Degeneration and hyperpigmentation of the basal layer is the main histopathologycal characteristics. Clinically, the chest and the proximal extremities are the anatomical areas commonly affected in this asymptomatic disease with chronic course. The clinical history and the physical examination are the basis of diagnosis, the biopsy of the skin active borders confirms it. Although there are several treatment options, only dapsone and clofazimine have shown efficacy in the ashy dermatosis treatment. Lichen planus pigmentosus and idiopathic eruptive macular pigmentation are two of the main differential diagnoses, the clinician should consider.

A Case of Pigmentary Glaucoma Due to Multidrug-Resistant Tuberculosis Treatment

PURPOSE: To report a case of secondary pigmentary glaucoma due to clofazimine treatment for extensive drug-resistant tuberculosis. CASE SUMMARY: A 23-year-old man presented with blurred vision in both eyes. The patient started to take clofazimine for extensive drug-resistant tuberculosis six months prior, after which his facial skin color changed to a dark-brown. Intraocular pressure (IOP) was 50 mm Hg in the right eye and 48 mm Hg in the left eye. Slit lamp examination revealed corneal edema, opacity, and flare in the anterior chamber in both eyes. A color vision test revealed a mild color defect in both eyes. Visual field (VF) test revealed superior temporal VF loss in the left eye. Gonioscopy revealed open angles with high pigmentation in the trabecular meshwork in both eyes. The patient was diagnosed with pigmentary glaucoma, and maximum tolerated medical therapy was performed. However, the IOP was uncontrolled. Trabeculectomy was performed in both eyes. Postoperative IOP was measured to be 12 mm Hg in both eyes without medication, and visual acuity measured 20/22 in the right eye and 20/17 in the left eye. CONCLUSIONS: To the best of our knowledge, this report is the first case of clofazimine being a possible cause of pigmentary glaucoma in a patient with extensive drug-resistant tuberculosis.

Clinical study of combination treatment with Clofazimine and others for patients with multidrug-resistant tuberculosis / 中国生化药物杂志

Objective To evaluate the clinical efficacy and safety of combination treatment with clofazimine ( Cfz ) and other antituberculosis drugs for patients with multidrug-resistant tuberculosis(MDR-TB).Methods 32 cases of MDR-TB patients were treated with combination regimens that included clofaziminefrom October 2011 to September 2016 in our hospitol,according to the history of drug use and drug susceptibility test results using individualized chemotherapy,the starting dose of clofazimine was 0.1 g/day,oral,some patients with adverse reactions and tolerance adjusted to 0.05 g/day,treatment for the last 12 months for three consecutive sputum mycobacterium tuberculosis culture and sputum smear acid-fast bacilli were cured,observe the clinical efficacy and safety.Results After treatment with the combined regimen,56.2%(18/32) of patients were cured,43.8%(14/32) of patients failed treatment, there was no statistically significant difference in the number of drug-resistant patients before and after CFZ treatment,there was no statistically significant difference between the time of failure and the time of CFZ treatment,after taking CFZ combined with anti-tuberculosis program,the number of drug users was statistically significant of patients cured and failed (P<0.05).The average time of sputum culture inversion was 16w.90.6% (29/32) of patients with adverse reactions,mainly including skin color change,ichthyosis and gastrointestinal tract and other adverse reactions, through dose adjustment and symptomatic treatment to continue treatment.The average duration of treatment with clofazimine was about 13 months.ConclusionClofazimine was welltolerated,combination treatment with Clofazimine and others for patients with MDR-TBhave better efficacy .

Dermatosis cenicienta: eritema discrómico perstans / Ashy dermatosis: erythema dyschromicum perstans

La dermatosis cenicienta o eritema discrómico perstans, fue descrita en El Salvador en 1957 por el Dr. Oswaldo Ramírez; desde entonces, se ha considerado como una hipermelanosis idiopática, adquirida, crónica y de evolución lenta, caracterizada por lesiones maculares de color azul grisáceo, similares a la ceniza. Afecta principalmente cara, cuello, tronco y extremidades. La mayoría de los casos han sido reportados en América latina y Asia, afectando a personas de piel oscura, ambos sexos y desde el año de edad hasta los 80 años. El diagnóstico es por correlación clínico-patológica, debido a la similitud con patologías como el liquen plano pigmentado y la pigmentación macular eruptiva idiopática. Desde su descubrimiento se han probado esquemas terapéuticos siendo el uso de dapsona y clofazimina las opciones que han alcanzado mayor eficacia. El caso clínico es el de una mujer de 41 años con lesiones grisáceas en cara, cuello y brazos, quien fue diagnosticada por dermatología como xerosis y liquen plano simple, durante tres años recibió manejo con cremas hidratantes, corticodes y antihistamínicos hasta que realizan biopsia de piel identificándose dermatosis cenicienta e iniciando tratamiento con clofazimida con mejoría notable.

The ashy dermatosis or erythema dyschromicum perstans was described by Oswaldo Ramírez from El Salvador in 1957. It is an acquired, chronic, idiopathic hypermelanosis of long-standing evolution that is characterized by blue-gray color macules that look like ash. It usually affects the face, neck, trunk, and extremities. Most of the cases have been reported in Latin America and Asia. It usually affects dark skin people of both sexes and from ages ranging from one to eighty years. The diagnosis is achieved by clinic-pathological correlation because of the similarities with other disease such as lichen planus pigmentosus and idiopathic eruptive macular pigmentation. Since its discovery, many therapeutic regimes have been tried, but dapsone and clofazimine are the most effective choices. The clinical case is about a 41 year old woman with gray lesions on the face, neck and arms, who was diagnosed by dermatologist like xerosis and lichen planus, handled for 3 years with moisturizers creams, corticosteroids and antihistamines until a biopsy specimen was taken, the ashy dermatosis was identified and the treatment with clofazimine was started, producing great improvement.

WBC count and functional changes induced by co-administration of clofazimine and clarithromycin, in single and multiple doses, in Wistar rats

Clofazimine and clarithromycin are used to treat leprosy and infections caused by Mycobacterium avium complex. Little data on the toxicity of co-administration of these two drugs are available. Here we evaluated the potential adverse effects of polytherapy with these two drugs in male Wistar rats by determining WBCs counts and other blood cell counts, neutrophilic phagocytosis, and burst oxidative, by flow cytometry. We observed an increase in WBCs, in multiple-dose regimens, and in polymorphonuclear cells, in both single- clarithromycin only and multiple dose regimens. We also observed a reduction in mononuclear cell counts in single and multiple doses. The drugs seem to reverse the mononuclear and polymorphonuclear cell ratio. An increase in oxidative burst was observed in animals treated with the drugs administered either individually or combined. In conclusion, clofazimine and clarithromycin change WBCs counts. Our results may contribute for a better understanding of the mechanisms related to the effects of co-administrating the two drugs.

Clofazimina e laritromicina são utilizadas no tratamento da hanseníase e em infecções causadas pelo complexo Mycobacterium avium. Devido à escassez de dados sobre a toxicidade de esquemas terapêuticos que associam estes fármacos, este estudo teve por objetivo avaliar os efeitos adversos desta terapia, em ratos machos Wistar, por meio da determinação da contagem global e específica de leucócitos e ensaios de fagocitose e burst oxidativo de neutrófilos por citometria de fluxo. Houve aumento do número de leucócitos (dose múltipla) e de células polimorfonucleares (doses única e múltipla) nos grupos tratados com claritromicina em monoterapia ou associada à clofazimina e redução das células mononucleares, em doses única e múltipla, nos mesmos grupos. Os fármacos parecem inverter a proporção entre células mono e polimorfonucleares. Observou-se aumento do burst oxidativo nos animais tratados com os fármacos isolados ou associados. Concluindo, clofazimina e claritromicina provocam alterações leucocitárias e os resultados podem contribuir para melhor entendimento dos mecanismos relacionados aos efeitos da administração dos fármacos em associação.

Pioderma gangrenoso associado à retocolite ulcerativa: relato de caso e revisão literária / Pyoderma gangrenosum associated with ulcerative retocolitis: case report and literature review

O Pioderma Gangrenoso é uma doença inflamatória da pele, cuja apresentação mais comum é através de úlceras necróticas nos membros inferiores. Seu diagnóstico clínico muitas vezes é de exclusão. Desde sua descoberta em 1930 até os dias atuais, ainda não há tratamento específico baseado em evidências sustentadas por estudos controlados e randomizados.Esta é uma revisão literária seguida de relato de caso de uma mulher de 41 anos, com Pioderma Gangrenoso na forma pustulosa e clássica, com boa resposta ao tratamento com Clofazimina, Azatioprina e Prednisona.

Pyoderma gangrenosum is an inflammatory disease of the skin which usually presents necrotic ulcer in lower limbs. Most of the time, there are no means of diagnosis but exclusion. Since its discovery in 1930 to nowadays there are no specific treatments based on evidence supported by randomized controlled trials. The authors make a literature review followed by a case report of a 41 year old women with pyoderma gangrenosum pustular type with typical presentation, treated successfully with Clofazimine, Azathioprine and Prednisone.

Treatment of Erythema Nodosum Leprosum (ENL) with high-dose Clofazimine in patients with Lepromatous Leprosy

ENL is a type ll leprosy reaction and occurs in people with borderline lepromatous and lepromatous leprosy, usually as a complication following treatment. The treatment of choice for ENL is prednisolone in view of its’ ready availability and affordability1. Howeve r, glucocorticoid therapy, even in low doses, can produce substantial toxicity. The risk is clearly greater as the dose increases. However, in cases where there are steroid-induced complications, high-dosed clofazimine may be used to reduce or withdraw corticosteroids in steroid-dependant cases2,3. We described 2 steroid-dependent ENL patients with steroid-induced complications who are successfully managed with the addition of highdosed clofazimine and the resultant weaning down of systemic glucocorticoids.

Alterações hematológicas, hemostáticas e bioquímicas induzidas pela clofazimina e claritromicina, em doses única e múltiplas, em ratos / Hematological, hemostatic and biochemical alterations induced by clofazimine and clarithromycin, in single and multiple doses, in rats

Claritromicina e clofazimina têm sido utilizadas no tratamento da hanseníase, tuberculose e infecções causadas pelo complexo Mycobacterium avium. Como os dados sobre a toxicidade de esquemas terapêuticos que incluem estes fármacos são escassos, este estudo teve como objetivo determinar os efeitos adversos destas terapias, por meio da avaliação dos parâmetros hematológicos, hemostáticos e bioquímicos. Os fármacos foram administrados em ratos machos Wistar, em monoterapia, em regime de doses única e múltipla. Claritromicina provocou aumento de leucócitos mono e polimorfonucleares. Ambos os fármacos inverteram a proporção entre células mono e polimorfonucleares e provocaram aumento do número de células polimorfonucleares e células em degeneração. Clofazimina e claritromicina prolongaram o tempo de protrombina e claritromicina também prolongou o tempo de tromboplastina parcial ativa. Claritromicina causou aumento de bilirrubinas total e direta e, ambos os fármacos, elevaram os níveis plasmáticos de gama-glutamiltransferase. Portanto, clofazimina e claritromicina induzem alterações hematológicas, hemostáticas e hepáticas.

Clarithromycin and clofazimine have been used to treat leprosy, tuberculosis and infections caused by the Mycobacterium avium complex. Since there is a scarcity of data on the toxicity of therapeutic regimens that include these drugs, this study had the aim of determining the adverse effects of these therapies, through evaluation of hematological, hemostatic and biochemical parameters. The drugs were administered to male Wistar rats, as monotherapy, in regimens of single and multiple doses. Clarithromycin caused increases in the numbers of mononuclear and polymorphonuclear leukocytes. Both of the drugs inverted the proportions between mononuclear and polymorphonuclear cells and increased the numbers of polymorphonuclear cells and degenerating cells. Clofazimine and clarithromycin prolonged the prothrombin time and clarithromycin also prolonged the activated partial thromboplastin time. Clarithromycin caused increases in total and direct bilirubin. Both of the drugs increased the plasma levels of gamma-glutamyltransferase. Therefore, clofazimine and clarithromycin induce hematological, hemostatic and hepatic changes.

Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseníase multibacilar / Therapeutic study comparing the association rifampin, ofloxacinand minocycline, with the association rifampin, clofazimine anddapsone in multibacillary leprosy patients

Foram comparados dois esquemas terapêuticos em pacientes com hanseníase multibacilar. O grupo controle com 14 pacientes recebeu o tratamento convencional.O grupo teste com 12 pacientes recebeu a associação de rifampicina 600 mg, ofloxacina 400 mg,e minociclina 100 mg, uma vez por mês, durante dois anos. Na avaliação inicial foram realizados exames clínicos, baciloscópicos e histológicos. A baciloscopia e a biópsia foram repetidas no final do primeiro e segundo ano de tratamento. As avaliações clínicas realizadas mensalmente. Todos pacientes apresentavam lesões cutâneas, que os caracterizavam como virchovianos ou peri-virchovianos. No grupo controle, o índice baciloscópico antes do tratamento variou de 2 a 4,8 e no grupo teste de 1,6 a 4,8. Histologicamente apresentavam quadro de hanseníase virchoviana ativa, exceto um paciente do grupo teste. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados,o índice baciloscópico diminuído e quadro histológico regressivo. Essa tendência se mantinha e ao final do segundo ano todos estavam clinicamente, baciloscopicamente e histologicamente ainda melhores. Análise estatística mostrou não haver diferença significante entre os grupos, sendo os esquemas equivalentes. No grupo controle todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados deste estudo demonstraram que o esquema com rifampicina, ofloxacinae minociclina, teve eficácia e segurança equivalente a poliquimioterapia convencional para multibacilar. Além disso, não causa pigmentação cutânea, pode ser totalmente supervisionado, podendo ser utilizado como esquema alternativo

Two therapeutic schemes in multibacillary leprosy patients were compared. The control group with 14 patients received the conventional treatment (MDT-MB). The test group with 12 patients, received the association rifampin 600 mg, ofloxacin 400 mg and minocycline 100 mg (ROM), administrated under supervision once a month, during two years. Initial evaluations include clinical, bacilloscopic and histological exams. The bacilloscopy and the biopsy were repeated at the end of first and second year of treatment. Clinical evaluations were performed monthly. All patients presented skin lesions characteristic of the lepromatous type. In the control group, the bacterial index (BI) before treatment ranged from 2 to 4.8 and in the test group it ranged from 1.6 to 4.8. Histological picture resembled active lepromatous leprosy, except one patient from the test group. At the end of the first year of treatment all patients showed clinical improvement, decreased BI and regressive histological picture. This tendency was maintained and at a final evaluation at the end of the second year all patients showed improvement on clinical, bacilloscopic and histological evaluations. Statistical analysis showed no significant differences between the groups, therefore, the two schemes were similar. In the control group all patients presented skin pigmentation after clofazimine intake. The results demonstrated that monthly administration of ROM is as efficacious and safe as MDT-MB. Besides, it doesn’t cause skin pigmentation, it can be given under supervision and can be used as alternative scheme.

Multi-drug resistant extra-pulmonary tuberculosis in a HIV negative patient.

A 25 year-old, HIV seronegative male presented with bilateral cervical lymphadenopathy with cold abscesses and sinus formation, peripancreatic lymphadenopathy and hypodense lesions in the spleen. Culture of pus aspirated from the cold abscess in the neck grew M.tuberculosis resistant to Rifampicin, Isoniazid, Ciprofloxacin and Para-aminosalicylic acid. In a resource-limited setting, he was treated with Ethambutol (E), Pyrazinamide (Z), Ethionamide (Eth), Cycloserine (Cyc), and Ofloxacin (Ofl). While on treatment, he developed drug induced hepatotoxicity; Z and Eth were stopped and clofazimine was added to the regimen. Subsequently, he developed splenic abscess and clofazimine induced generalized pigmentation of the body including tongue. After eighteen months of treatment, lymphadenopathy and splenic lesions regressed significantly. Thus, present case highlights several important basic principles of management of MDR-TB such as procuring tissue for microbiological testing, judicious use of imaging modalities, careful monitoring for adverse drug reactions, intercurrent infections and the need for pretreatment counselling for ensuring compliance and completion of treatment.

A case of Melkersson-Rosenthal syndrome / 대한피부과학회지

Melkersson-Rosenthal syndrome(MRS) is a rare neuro-muco-cutaneous disease of unknown origin. The classic triad of this clinically defined entity consists of orofacial swelling, facial nerve palsy, and lingua plitica. MRS may occur as a complete triad of symptoms or a combination of any features of the classic triad, termed monosymptomatic and oligosymptomatic forms. The complete triad has been reported to occur in only 10% to 20% in different series. Because of the rarity of reported cases in Korea, we report a case of complete form of MRS, in which clofazimine showed a partial response.

A Case of Pyoderma Gangrenosum Treated with Clofazimine / 대한피부과학회지

We present herein a case of pyodcrma gangrenosum, who showed good response to clofazimine therapy. The patient, 19-year-old male, had suffered from chronic diarrhea for 10 months before the rapidly spreading pustules and ulcers with undermined purple-to-red borders devkloped on his both lower and upper extremitics. Clofazimine was given orally in a dose of 100mg three times daily for 16 days, and tapered to 100 mg two times daily for the next 11 days. Clinical improvement was noted after 7 day's treatment and the almost all of the skin lesiors were replaced by granulation tissue with epithelizatiori or crust formation after 6 days treatment.

The Change of Bacillary Index after Combined Treatment of Dapsone and Clofazimine in Leprosy / 대한피부과학회지

Seventy-seven patients who were treated regularly for more than 5 years in the Taegu Leprosy Mission were investigated with regard to the change of the bacillary index(BI) after treatment of either dapsone(DDS) alone or a combination of DDS and clofazimine. The results were as follows: 1) In the group that took only DDS 400-500 mg per week, the BI conversion to negative took average 51 months. 2) In the group that took only 600-700 mg per week, the BI conversion to negative took average 34 months. 3) In the group that took only DDS 400 mg per week initially and 600-700mg per week secondarily, the BI conversion to negative took average 64 months, the last 33 months of which marked the time period that 600-700 mg were taken per week. 4) In the group that took only DDS 400-500mg per week initially and a combination of DDS gpp 700 mg per week and clofazimine. 3pp-4pp mg per week secondarily, the BI conversion to negative took average 63 months, the last 35 months of which marked the time period for the combined therapy. 5) In the group that took a combination of DDS 600- 700 mg per week and clofazimine 400 mg per week, the BI conversion to negative took average 42 months.