RESUMEN
The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1ß, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1ß, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.
Asunto(s)
Carbono/metabolismo , Cistationina gamma-Liasa/fisiología , Sulfuro de Hidrógeno/toxicidad , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/etiología , Alquinos/farmacología , Animales , Cistationina gamma-Liasa/antagonistas & inhibidores , Citocinas/metabolismo , Inhibidores Enzimáticos/farmacología , Glicina/análogos & derivados , Glicina/farmacología , Glucólisis , Sulfuro de Hidrógeno/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Linfocitos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mycobacterium tuberculosis/efectos de los fármacos , Células Mieloides/efectos de los fármacos , Células Mieloides/inmunología , Células Mieloides/metabolismo , Transducción de Señal , Tuberculosis Pulmonar/metabolismo , Tuberculosis Pulmonar/patologíaRESUMEN
BACKGROUND AND AIM: The aim of this study was to assess the prevalence and characteristics of celiac disease (CD) in all patients with type 1 diabetes mellitus attending a tertiary adult diabetes clinic in Durban, South Africa. METHODS: This was a cross-sectional observational study that screened 202 patients; of these, 56.4% were African (Black), 31.7% Asian Indian, 4.5% White, and 7.4% mixed race. Demographic data, symptoms, and anthropometry were documented. Blood tests included anti-tissue transglutaminase antibody (tTG), anti-endomysial antibody (EMA), and anti-gliadin antibody (AGA). Endoscopy and duodenal biopsy were performed in patients with celiac antibodies. Diagnosis of CD was based on the modified Marsh classification. RESULTS: Mean age and mean duration of diabetes were 26.4 ± 11.4 and 10.7 ± 9.1 years, respectively. Celiac antibodies were found in 65 (32.2%) patients: EMA 7.4%, tTG immunoglobulin A (IgA) 8.4%, tTG immunoglobulin G 1.9%, AGA IgA 18.3%, and AGA immunoglobulin G 21.8%. Histological evidence of CD was found in 5.9% (n = 12/202): 2.5% were classed as definite CD (Marsh 3) and 3.4% as potential CD (Marsh 1). None of the patients with CD were symptomatic. The sensitivity of AGA IgA, EMA, and tTG IgA antibodies for detecting histologically proven CD was 66.7%, 50.0%, and 41.7%, respectively. CONCLUSION: The prevalence of CD was similar to reports from western countries. No ethnic specific differences were noted. CD was silent in all patients in this study. The sensitivity of EMA and tTG antibodies was poor and merits further evaluation as screening tools for CD in South African patients with type 1 diabetes mellitus.
Asunto(s)
Enfermedad Celíaca/epidemiología , Diabetes Mellitus Tipo 1/epidemiología , Adolescente , Adulto , Biomarcadores/sangre , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/etnología , Niño , Estudios Transversales , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/etnología , Femenino , Proteínas de Unión al GTP/inmunología , Gliadina/inmunología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Prevalencia , Proteína Glutamina Gamma Glutamiltransferasa 2 , Grupos Raciales , Sudáfrica/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Transglutaminasas/inmunología , Adulto JovenRESUMEN
OBJECTIVE: Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. RESEARCH DESIGN AND METHODS: This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B12, folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. RESULTS: A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1â years, respectively. Mean body mass index was 21.6±6.3â kg/m2. GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves' disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). CONCLUSIONS: Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required.
Asunto(s)
Autoanticuerpos/sangre , Autoantígenos/sangre , Diabetes Mellitus Tipo 1/sangre , Yoduro Peroxidasa/sangre , Proteínas de Unión a Hierro/sangre , Células Parietales Gástricas/inmunología , Adolescente , Adulto , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/etnología , Estudios Transversales , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/etnología , Femenino , Humanos , Masculino , Prevalencia , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: Idiopathic membranous nephropathy (IMN) is a rare form of childhood nephropathy. To date there are no standardized protocols of management for this condition in children. The aim of this study is to report on 4 children with IMN who were treated with mycophenolate mofetil (MMF). METHODS: MMF was given in combination with low dose steroids and angiotensin converting enzyme antagonists in a dose of 1,200 mg/m2 body surface area in two divided doses for a minimum of 6 months. RESULTS: All children had histopathological findings in keeping with Stage III membranous nephropathy. At the last hospital visit, 3 children had achieved a > 50% reduction of proteinuria with preservation of renal function. One patient who failed to respond progressed to Stage III chronic kidney disease. None of the children who were treated with MMF experienced any major side effects of the drug. CONCLUSIONS: MMF, administered over a limited period, served as a safe and effective immunosuppressive agent in the treatment of this condition, in conjunction with low dose steroids and angiotensin converting enzyme inhibitors. Large multicenter randomized studies of children with IMN are necessary to assess the efficacy and long term safety of MMF.
Asunto(s)
Glomerulonefritis Membranosa/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Corticoesteroides/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Niño , Preescolar , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Ácido Micofenólico/uso terapéuticoRESUMEN
Bacillary angiomatosis (BA) is an increasingly reported infection, mainly in patients with acquired immunodeficiency syndrome. Different epidemiological risk factors are associated with the transmission of the causative agents, Bartonella henselae and B. quintana. Vulval BA is described rarely. Two patients presented with a vulval mass (Patient 1) and a verrucous vulval growth (Patient 2), which were diagnosed clinically as tuberculosis and carcinoma, respectively. Patient 1 also had pulmonary tuberculosis and Kaposi sarcoma. Biopsy of the vulval lesions confirmed BA, characterized by a multilobular proliferation of blood vessels that were lined by epithelioid endothelial cells. There were prominent intervascular neutrophils, karyorrhectic debris, and clumps of paravascular argyrophilic organisms. The biopsy from Patient 1 was deep dermal/subcutaneous in location and displayed foci of confluent suppuration. There was florid pseudoepitheliomatous hyperplasia in the biopsy from Patient 2. Molecular investigations confirmed intralesional B. quintana, hitherto unreported in vulval BA, as the causative agent in both biopsies. On follow-up, Patient 2 had developed additional lesions in the vulva and thigh, but all her lesions and the vulval mass (Patient 1) responded to erythromycin treatment. Patient 1 succumbed to tuberculosis. Heightened recognition of BA underpins rapid and optimal clinicopathological diagnosis, even in uncommon locations. Identification of the causative Bartonella species is important for appropriate, interventive social management.
Asunto(s)
Angiomatosis Bacilar/patología , Bartonella quintana/crecimiento & desarrollo , Neoplasias de la Vulva/microbiología , Adulto , Angiomatosis Bacilar/microbiología , Bartonella quintana/genética , Biopsia , ADN Bacteriano/química , ADN Bacteriano/genética , Resultado Fatal , Femenino , Histocitoquímica , Humanos , Reacción en Cadena de la Polimerasa , Neoplasias de la Vulva/patología , Adulto JovenRESUMEN
BACKGROUND: Despite the burden of human immunodeficiency virus (HIV) disease in Southern Africa, there have been few reports of HIV-related nephropathy in children. This study outlines the spectrum of HIV-1-related kidney diseases of children in KwaZulu-Natal, South Africa. METHODS: A review of the clinical presentation, laboratory and histopathological findings of children diagnosed with HIV-related nephropathy. RESULTS: Forty-nine out of 71 children (1-16 years old) with HIV-1 related nephropathy underwent kidney biopsy. The most common histopathological finding was focal segmental glomerulosclerosis (FSGS), which was present in 32 (65.3%) children; 13 (26.5%) having collapsing glomerulopathy and 19 (38.8%) classic FSGS. The majority of patients showed haematological (86.4%) and electrolyte abnormalities (69.4%). Renal impairment was present in 41% of patients on initial presentation. However, end-stage kidney disease was present in only 4% of these patients. All patients were treated with highly active anti-retroviral therapy (HAART), the majority (79.6%) showed decreased proteinuria with 38.8% having complete remission. CONCLUSIONS: This study, one of the largest series of children reported from Africa, demonstrates that nephrotic syndrome due to HIV-associated nephropathy (HIVAN) is the commonest presentation of HIV-related nephropathy in childhood. Highly active anti-retroviral therapy in combination with angiotensin-converting enzyme antagonists is highly effective in decreasing proteinuria and preserving renal function.
Asunto(s)
Nefropatía Asociada a SIDA/fisiopatología , Nefropatía Asociada a SIDA/complicaciones , Nefropatía Asociada a SIDA/patología , Adolescente , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Terapia Antirretroviral Altamente Activa , Western Blotting , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Glomeruloesclerosis Focal y Segmentaria/etiología , Glomeruloesclerosis Focal y Segmentaria/patología , Trastornos del Crecimiento/etiología , Infecciones por VIH/epidemiología , Seropositividad para VIH , Humanos , Lactante , Riñón/patología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/patología , Pruebas de Función Renal , Masculino , Síndrome Nefrótico/etiología , Proteinuria/tratamiento farmacológico , Proteinuria/etiología , Sudáfrica/epidemiología , Carga ViralRESUMEN
Two infants, 6 months and 4 months of age, presented with bilateral or unilateral external auditory canal polyps and otorrhea, respectively. Additional findings on examination included otitis media and mastoiditis. Tympanic membrane perforation was noted in one patient and a postauricular abscess in the other. Incisional biopsies of the polyps and abscess were reported as nonspecific mixed inflammation and abscess wall, respectively. There was a limited response to an empirical 5-day course of trimethoprim sulfamethoxazole. The children were referred to the academic hospital, and excision of the polyps and biopsies of the middle ear, mastoid, and postauricular abscess was undertaken. All the biopsies demonstrated donovanosis. Reappraisal of the initial incisional biopsies also confirmed donovanosis. Trimethoprim sulfamethoxazole was administered to both patients for 3 weeks, with resolution of the lesions. Subsequent investigations confirmed genital tract donovanosis, human immunodeficiency virus seropositivity, acquired immunodeficiency syndrome, and pulmonary tuberculosis in both mothers. Heightened awareness of the occurrence of donovanosis at unusual sites and improved recognition of the histomorphological features of the disease, especially in small and superficial biopsies, are pivotal not only for its correct diagnosis in extragenital cutaneous and extracutaneous locations but also for timely and adequate therapy and an improved infant and maternal outcome.
Asunto(s)
Conducto Auditivo Externo/patología , Enfermedades del Oído/patología , Granuloma Inguinal/patología , Transmisión Vertical de Enfermedad Infecciosa , Pólipos/patología , Antiinfecciosos/uso terapéutico , Enfermedades del Oído/tratamiento farmacológico , Enfermedades del Oído/etiología , Femenino , Granuloma Inguinal/tratamiento farmacológico , Granuloma Inguinal/etiología , Humanos , Lactante , Masculino , Pólipos/tratamiento farmacológico , Pólipos/etiologíaAsunto(s)
Seropositividad para VIH/complicaciones , VIH-1 , Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico , Neoplasias Pulmonares/patología , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Adulto , Antirretrovirales/efectos adversos , Antirretrovirales/uso terapéutico , Recuento de Linfocito CD4 , Diagnóstico Diferencial , Disnea/etiología , Seropositividad para VIH/tratamiento farmacológico , Humanos , Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/etiología , Masculino , Radiografía , Sarcoma de Kaposi/etiología , Piel/patología , Neoplasias Cutáneas/etiología , Tuberculosis Pulmonar/diagnósticoRESUMEN
AIMS: AIDS-associated myoid tumours (AIDS-MTs), often Epstein-Barr virus (EBV)-associated (EBV-positive MTs), include smooth muscle tumors (SMTs) and the relatively recently recognized myopericytomas (MPCTs). The myoid immunophenotype of AIDS-MTs has been documented inconsistently. The aim of this study was to reappraise the phenotypic and immunophenotypic features of extra-uterine AIDS-MTs and the clinical profile of afflicted patients. METHODS AND RESULTS: EBV early RNA in-situ hybridization testing on 27 AIDS-MTs from 25 patients identified 19 of 27 (70.4%) EBV-positive MTs and eight of 27 (29.6%) EBV-negative MTs. EBV-positive MTs comprised 12 of 19 EBV-positive SMTs [six leiomyomas, one smooth muscle tumour of uncertain malignant potential (STUMP), five leiomyosarcomas] and seven of 19 EBV-positive MPCTs [benign (five), malignant (two)]. The EBV-negative MTs, made up exclusively of EBV-negative SMTs, included angioleiomyoma (one), leiomyoma (one), STUMP (one) and leiomyosarcomas (five). Malignant AIDS-MTs demonstrated hypercellularity, pleomorphism, increased mitoses and necrosis. EBV-positive leiomyosarcomas retained a conspicuous fascicular architecture. Four of five EBV-negative leiomyosarcomas demonstrated marked pleomorphism. All EBV-positive MPCTs and two EBV-positive leiomyosarcomas contained aggregates of desmin-negative round and oval cells. Seventeen of 25 patients died, mainly from comorbid diseases. CONCLUSION: While the reappraised spectrum of AIDS-MTs does not demonstrate divergent subtype-determined clinical behaviour, heightened awareness/recognition of this expanded spectrum will not only promote improved diagnosis of pleomorphic and myopericytic variants, which may be the sentinel clue to AIDS and its comorbidity, but will also facilitate distinction from histopathological mimics in specific anatomic locations.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/complicaciones , Neoplasias de Tejido Muscular/patología , Neoplasias de Tejido Muscular/virología , Adulto , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Humanos , Hibridación in Situ , Masculino , Persona de Mediana Edad , Pericitos/patología , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: We describe a series of previously unreported, distinctive, polypoid solitary T-cell-rich cutaneous pseudolymphomas. METHODS: The clinicopathologic features were examined in 17 cases. RESULTS: Patient ages ranged from 16 to 71 years (mean = 38.5) with a female predominance (female : male = 14 : 3). All lesions, clinically diagnosed most often as pyogenic granuloma, presented as a solitary, polypoid, erythematous, papule ranging in size from 2.5 to 7.5 mm (mean = 5.8). Most occurred on the head and neck (7) and trunk (6) with other sites including the thigh (1), shoulder (1) and knee (1). A dense dermal infiltrate composed of mildly atypical lymphocytes with variable numbers of admixed plasma cells and histiocytes was prototypical. Commonly, there was an associated epidermal collarette (16/17), Grenz zone (11/17) or admixed eosinophils (8/17). Prominent vessels lined by plump endothelial cells, reminiscent of high endothelial venules of lymph nodes, were universal and some degree of telangiectasia was also common (12/17). CD3-positive T-cells consisted of an admixture of CD4-positive and CD8-positive forms (15/16). Multiple studies suggested polyclonality (seven cases). No recurrences after lesional excision were noted in the 17 patients with a follow-up range from 24 to 120 months (mean = 46.6). CONCLUSION: Although these lesions share histopathologic features of the so-called acral pseudolymphomatous angiokeratoma of children (APACHE), they occur in a completely different clinical setting, present in solitary and polypoid fashion and are T-cell rich. We propose the diagnostic label T-cell-rich angiomatoid polypoid pseudolymphoma for this distinctive but presumably reactive lesion.
Asunto(s)
Seudolinfoma/clasificación , Seudolinfoma/patología , Enfermedades de la Piel/clasificación , Enfermedades de la Piel/patología , Linfocitos T/patología , Adulto , Anciano , Antígenos CD/biosíntesis , Biomarcadores/análisis , Femenino , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.
Asunto(s)
Células de Langerhans/patología , Sarcoma de Kaposi/patología , Adulto , Biomarcadores de Tumor/análisis , Diagnóstico Diferencial , Femenino , Infecciones por VIH/complicaciones , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de la Vaina del Nervio/patología , Fenotipo , Proteínas S100/metabolismo , Sarcoma/patología , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virología , Adulto JovenRESUMEN
Although rare in childhood, a relatively high incidence of smooth muscle tumors are recognized in patients with AIDS, mainly in association with Epstein Barr virus (EBV) infection. Although EBV-associated smooth muscle tumors have been documented rarely in the subcutis of AIDS patients, dermal involvement has not been described to date. This report describes dermal EBV-associated leiomyosarcomas (EBV-LMS) with a nodular but superficial plaque-like appearance on the lower limbs of 2 males, 9 and 12 years old. Histopathological assessment of the excised lesions demonstrated hypercellular mitotically active dermal tumors with hyperchromatic spindle and round cells, arranged in short fascicles and sheets, with microfoci of necrosis. A smooth muscle immunophenotype, including prominent desmin immunopositivity, and positive EBV-encoded RNA in situ hybridization investigation confirmed a diagnosis of EBV-LMS. Subsequent HIV seropositivity and AIDS were confirmed in both patients. Both patients also had pulmonary tuberculosis and received antituberculous therapy. Patient 1 had a 3 cm re-excision of the prior tumor site. He received highly active antiretroviral therapy, completed 6 months of antituberculous therapy, achieved immune reconstitution and viral suppression and is tumor-free 2 years after tumor excision. Patient 2 died before further therapy. The immune status, presence, and appropriate therapy of co-existent systemic infection and highly active antiretroviral therapy in AIDS patients with EBV-LMS are crucial to a favorable outcome.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/patología , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/aislamiento & purificación , Leiomiosarcoma/patología , Neoplasias Cutáneas/patología , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4/genética , Humanos , Huésped Inmunocomprometido , Leiomiosarcoma/cirugía , Leiomiosarcoma/virología , Masculino , ARN Viral/análisis , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/virologíaRESUMEN
The histopathological assessment of cutaneous lesions is critical to the definitive diagnosis of many human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome-associated dermatoses, infections and tumours. Dermatopathological challenges stem mainly from the altered histopathological profile of established cutaneous entities compared with that in the HIV-unaffected population, the emergence of new diseases and the impact of therapeutic modalities on cutaneous lesions. This review focuses on some of these diagnostic dilemmas, with emphasis on the following challenges: (i) infective diagnostic pitfalls; (ii) itchy papular skin lesions; (iii) co-lesional comorbid diseases; (iv) drug-induced disease alterations; and (v) neoplastic and pseudoneoplastic proliferations. The drug-induced alterations include highly active antiretroviral therapy-associated disease modifications.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/complicaciones , Enfermedades de la Piel/etiología , VIH , Infecciones por VIH/patología , Humanos , Enfermedades de la Piel/patologíaRESUMEN
BACKGROUND: Co-lesional acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma (AIDS-KS) and Mycobacterium tuberculosis-associated granulomatous inflammation are undocumented. METHOD: Retrospective appraisal of skin biopsies with co-lesional AIDS-KS and microscopic tuberculosis (TB). RESULTS: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non-necrotizing and a combination of necrotizing and non-necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl-Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co-lesional TB in 15/16 biopsies. Co-lesional AIDS-KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. CONCLUSION: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co-lesional occurrence of AIDS-KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/microbiología , Granuloma/microbiología , Mycobacterium tuberculosis , Sarcoma de Kaposi/microbiología , Neoplasias Cutáneas/microbiología , Síndrome de Inmunodeficiencia Adquirida/complicaciones , Síndrome de Inmunodeficiencia Adquirida/patología , Adulto , Femenino , Granuloma/complicaciones , Granuloma/patología , Humanos , Masculino , Estudios Retrospectivos , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patologíaRESUMEN
Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a relatively recently described gastric tumor with a peculiar plexiform growth pattern. PAMT is typified by a myofibroblastic immunophenotype that distinguishes it from the more common gastrointestinal stromal tumors and the rarely documented fibromyxomas. We report an additional PAMT, the seventh tumor with this label, which was an incidental finding on abdominal computed tomography scan of a 35-year-old Indian female. The tumor measured 4 x 3 x 2 cm and demonstrated plexiform architecture, myxoid stroma, prominent vasculature and spindled cells with myofibroblastic differentiation. The clinicopathological features, progesterone immunopositivity, hitherto undocumented, and mimicry of other primary and secondary gastric mesenchymal tumors, including endometrial stromal sarcoma, are discussed.
Asunto(s)
Neoplasias de Tejido Muscular/diagnóstico , Neoplasias de Tejido Muscular/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Adulto , Diagnóstico Diferencial , Femenino , Fibroma/diagnóstico , Fibroma/patología , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/patología , HumanosRESUMEN
The clinicopathologic features of 4 AIDS patients with cutaneous colesional Kaposi sarcoma (KS) and cryptococcosis, a rare phenomenon, are described. Biopsies from 3 patients who were highly active antiretroviral therapy (HAART)-naive demonstrated predominant KS with a conspicuous spindle cell component and small aggregates of cryptococcal yeasts in 2 biopsies and predominant gelatinous cryptococcosis with attenuated KS spindle cells in 1 biopsy. One patient was HAART exposed. He had childhood pulmonary tuberculosis, was treated for disseminated cutaneous cryptococcosis 18 months earlier and presented with cutaneous lesions, odynophagia and massive cervical lymphadenopathy in the eighth week of HAART, after achieving viral suppression and a CD4 cell increase from 28 to 184 cells/µL. His skin biopsy demonstrated a dense lymphoplasmacytic infiltrate, neutrophils, and granulomas with admixed aggregates and single Cryptococcus neoformans and focal aggregation of human herpes virus 8-immunopositive spindle cells. Acid fast bacilli were not identified and mycobacterial molecular studies were negative. The features were compatible with cutaneous cryptococcal immune reconstitution inflammatory syndrome. His nodal and oropharyngeal biopsies demonstrated dense mixed, including granulomatous, inflammation with few cryptococcal yeasts and acid fast bacilli, confirmed to be Mycobacterium tuberculosis on polymerase chain reaction testing, without KS. These features were also compatible with immune reconstitution inflammatory syndrome, but the exact role of each infection in the extracutaneous sites was unconfirmed. Colesional KS and cryptococcosis served as the sentinel lesion of AIDS in 3 patients and of immune reconstitution inflammatory syndrome in 1 patient.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Criptococosis/patología , Dermatomicosis/patología , Síndrome Inflamatorio de Reconstitución Inmune/patología , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Piel/patología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Antifúngicos/uso terapéutico , Terapia Antirretroviral Altamente Activa , Biopsia , Criptococosis/tratamiento farmacológico , Criptococosis/inmunología , Criptococosis/microbiología , Cryptococcus neoformans/aislamiento & purificación , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/inmunología , Dermatomicosis/microbiología , Femenino , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/inmunología , Síndrome Inflamatorio de Reconstitución Inmune/microbiología , Masculino , Persona de Mediana Edad , Sarcoma de Kaposi/inmunología , Sarcoma de Kaposi/virología , Piel/inmunología , Piel/microbiología , Piel/virología , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/virología , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To document the clinicopathological features of paediatric intussusception caused by acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS). METHODS: Clinicopathological features of six patients with AIDS-KS-associated intussusception were obtained retrospectively from departmental and hospital records. RESULTS: Six debilitated male children, without cutaneous KS, were presented with abdominal pain and vomiting for >1 week. Intussusception was the sentinel of HIV infection in five patients. One patient had been on HAART for 13 months. Three patients each had ileal and ileocolic intussusceptions; two had recurrent intussusception. Bowel resection was performed because of failed reduction, infarction and polypoid lead points in all patients, in addition to perforation and peritonitis in three. Five patients died, the immediate cause being massive hematochezia from anorectal KS and/or septic shock. One patient, who received post-surgical chemotherapy and HAART, is currently in remission. Pathologic examination confirmed intussusception due to KS. CONCLUSION: AIDS-KS-associated intussusception occurred without cutaneous KS. Resection of the infarcted segment may relieve the presenting obstruction, but recurrent intussusception may occur because every elevated KS is a potential lead point. AIDS-KS-I is rare but fatal in children, unless timely surgical intervention, optimal histopathological diagnosis, and appropriate medical management, including HAART and chemotherapy, are facilitated.
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Síndrome de Inmunodeficiencia Adquirida/complicaciones , Intususcepción/etiología , Sarcoma de Kaposi/complicaciones , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Terapia Antirretroviral Altamente Activa , Preescolar , Humanos , Intususcepción/mortalidad , Intususcepción/cirugía , Masculino , Estudios Retrospectivos , Sarcoma de Kaposi/mortalidadRESUMEN
BACKGROUND: Palisading granulomatous reactions are documented in many diseases. Although subcutaneous cystic echinococcosis (CE) is documented rarely, a subcutaneous palisading, granulomatous, pseudocystic (PGP) reaction to elusive Echinococcus granulosus membranous components, in the absence of cutaneous fistulization, is undocumented. METHODS: Seven-year clinicopathological review of subcutaneous echinococcal PGP reactions. RESULTS: Gross: seven thick-walled 'cysts' containing clear or straw-colored fluid were investigated. Histopathology: the pseudocysts contained a palisade of epithelioid histiocytes and giant cells. Focal periodic acid Schiff (PAS)-positive eosinophilic fragments, some resembling keratin 'flakes', were identified within the lumen or within the cellular palisade, consistent with a PGP reaction to fragmented E. granulosus membrane. Clinical correlation: the initial histopathological diagnosis of two patients was ruptured epidermoid cysts with an assumed granulomatous reaction to eosinophilic keratinous debris. Subsequent diagnosis of CE in the liver and cervical soft tissue necessitated review of the 'epidermoid cysts'; PAS-positive E. granulosus membranous fragments masqueraded as keratinous debris. Renal, hepatic and pleuropulmonary CE were confirmed in the remaining patients following confirmation of an echinococcal PGP reaction. CONCLUSION: Heightened awareness and obsessive appraisal of subcutaneous PGP reactions for subtle, focal, PAS-positive and echinococcal membranous fragments are pivotal to the diagnosis that also serves as a clue to visceral CE.
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Equinococosis/patología , Echinococcus granulosus , Granuloma Eosinófilo/patología , Quiste Epidérmico/patología , Granuloma de Células Gigantes/patología , Enfermedades Cutáneas Parasitarias/patología , Adulto , Animales , Quiste Epidérmico/parasitología , Epidermis/parasitología , Epidermis/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Even in schistosomiasis-endemic areas, extra-anogenital bilharziasis cutanea tarda (E-BCT) is rare. To date, the occurrence of E-BCT in pre-existing cutaneous pathology is undocumented. The study was undertaken to document the expanded clinicopathological spectrum and to comment on the putative pathogenetic mechanisms of a Schistosoma hematobium-associated E-BCT. METHODS: Eight-year clinicopathological appraisal of E-BCT. RESULTS: The clinical details are as follows. Seventeen specimens from 16 patients formed the study cohort. All specimens showed granulomatous inflammation with eosinophils, aggregates of terminal-spined S. hematobium ova and variable fibrosis. Copulating worms were identified in three biopsies. In 12/16 patients, E-BCT occurred in pre-existing pathology, including recurrent squamous papilloma (1), bilateral hidradenitis suppurativa (1) and scar tissue (10) with 7 showing a keloidal morphology. Prior and current urinary schistosomiasis was present in nine and seven patients, respectively. CONCLUSION: E-BCT, a reflection of prior, re-infective or inadequately treated urinary schistosomiasis, is deemed to be a function of egg-laying consequent to the aberrant pathway of worms. Based on E-BCT occurrence in pre-existing extra-anogenital cutaneous fibroinflammatory and cicatricial processes and the presence of adult worms in three extra-anogenital biopsies in the present study, it is hypothesized that altered tissue mesenchymal repair reactions may promote extra-anogenital cutaneous worm entrapment and egg-laying.
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Schistosoma haematobium , Esquistosomiasis/patología , Enfermedades Cutáneas Parasitarias/patología , Adolescente , Adulto , Animales , Biopsia , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We describe concomitant granuloma inguinale (GI) and malacoplakia of the cervix in 2 acquired immune deficiency syndrome (AIDS) patients aged 27 and 36 years. Both patients presented with a bloody foul-smelling vaginal discharge. Speculum examination confirmed cervical ulceration, prompting the diagnosis of cervical carcinoma in both patients. Cervical punch biopsies confirmed the characteristic features of GI; granulation tissue containing a dense plasma cell infiltrate, aggregates of neutrophils, and vacuolated enlarged histiocytes containing Donovan bodies were noted. Many of these histiocytes and sheets of von Hansemann cells contained intracytoplasmic Michaelis-Gutmann bodies, confirming concomitant malacoplakia. Michaelis-Gutmann bodies were also present in extracellular locations. Ultrastructural examination confirmed these histopathologic findings. One patient died of disseminated tuberculosis before treatment was initiated. The other patient did not return for a follow-up visit of her cervical lesion. Concomitant GI and malacoplakia is unreported in genital and extragenital sites; Klebsiella granulomatis must therefore be added to the list of bacteria associated with malacoplakia. Malacoplakia of the female genital tract is documented rarely and remains unreported, to date, in AIDS patients. Similar to the pathogenetic mechanisms described for AIDS-associated malacoplakia in extragenital sites, it is hypothesized that, in addition to abnormal macrophage functioning and an inability to degrade bacteria, special constituents of K. granulomatis are undigestable by lysosomal enzymes in human immunodeficiency virus-infected patients.