Diabetic mastopathy is a rare fibroinflammatory breast disease characterized by lymphocytic lobulitis, ductitis, and perivasculitis with stromal fibrosis. This lesion often presents as a discretely palpable uni- or bilateral mass in long-standing type I diabetes and other autoimmune diseases. We report a case of insulin-dependent diabetic mastopathy, which presented clinically as an indeterminate breast lump suspicious for malignancy. The patient is a 36-year-old woman who had type 1 insulin-dependent diabetes mellitus. Mammography and ultrasonography raised a suspicion of malignancy, and an excisional biopsy was performed. A previous biopsy had shown no evidence of malignancy. Histopathological examination now showed dense keloid-like stromal fibrosis with epithelioid-like and spindly myofibroblasts and a characteristic lymphocytic infiltration around blood vessels in and around lobules and ducts, features consistent with diabetic mastopathy. The literature is briefly reviewed.
Diabetic mastopathy; Insulin-dependent; Breast cancer; Pseudomalignancy
Lymphocytic mastopathy or diabetic mastopathy is a benign breast disease characterized by dense fibrosis, lobular atrophy, and aggregates of lymphocytes in a periductal and perilobular distribution. The condition usually affects women with a long history of diabetes mellitus (DM) and also those with autoimmune disorders. While the pathogenesis is unknown, a particular type of class II human leukocyte antigen has been associated with this disease. Herein, we report a case of diabetic mastopathy which clinically and radiologically mimicked primary breast neoplasms. The patient was a 74-year-old woman with a 31-year history of DM type II who presented with multiple firm lumps in bilateral breasts. Findings from mammography, ultrasonography, and magnetic resonance imaging of the breasts revealed an abnormal appearance which suspiciously resembled malignancy. An aspiration cytology specimen showed atypical accumulation of lymphoid cells, leading us to suspect lymphoma. Histology of an excisional biopsy showed the characteristic appearance of lymphocytic mastopathy, which predominantly consisted of B-lymphocytes. Autoantibodies in her serum reacted positively against her ductal epithelium as well as other diabetic and nondiabetic breast ductal cells. An antigen absorption test with insulin revealed attenuating intensity according to insulin concentration. These anti-insulin antibodies produced in the DM patient may cause ductitis because of antigen cross-reactivity.
Diabetic mastopathy is an uncommon, benign disease of the breast that can occur in women with diabetes and clinically mimic breast cancer. We describe a patient with long-standing type 1 diabetes who presented with a palpable breast mass with negative imaging findings on mammography, ultrasonography, and breast MRI. Surgical biopsy and histopathology confirmed diabetic mastopathy. We use this case to highlight the recognition, radiographic features, pathology, and management of this benign breast condition and emphasize that, in diabetic patients, the differential diagnosis of a new breast mass should include diabetic mastopathy.
BRCA mutation carriers have a life-long breast cancer risk between 55 and 85% and a high risk of developing breast cancer at a very young age, depending on the type of mutation. The risk of developing contralateral breast cancer after a first breast cancer is elevated up to 65%, especially in case of BRCA1 mutation and young age at the first breast cancer. Since bilateral prophylactic mastectomy is associated with a risk reduction of 90–95% of developing primary or contralateral breast cancer, this option is a key point within the counseling process for patient information and shared decision-making of mutation carriers. Although the local control after breast-conserving therapy in mutation carriers seems to be comparable to that of sporadic breast cancer patients, individual patient information and counseling should include all alternative procedures of oncologically adequate mastectomy techniques and immediate reconstruction. Excellent cosmetic results, high levels of life quality, and good patient acceptance can be achieved with the recent developments in reconstructive surgery of the breast.
BRCA mutation carrier; Mastectomy techniques; Reconstructive surgery of the breast; Prophylactic mastectomy
An Israeli Jewish population group consisting of 1298 cases of breast cancer and 1816 cases of benign mastopathy hospitalized in 1960-64 and 10,604 properly selected control women was studied with respect to the relationship of breast diseases to ethnic origin, educational background and socio-economic status. It was found that the percentage of Israeli-born and Orientals was higher in the benign mastopathy group than in the cancer group. For the Westerners the opposite was true. Educational level and socio-economic status were considerably higher in patients than in controls, regardless of ethnic origin. They were also higher in Westerners than in Orientals and among the Orientals higher in Iraqis than in Yemenites. The population groups with high breast cancer incidence rate appear to be on a higher educational and socio-economic level than those with a low incidence rate.
Leptin, an adipocyte-secreted hormone, regulates energy homeostasis as well as reproductive, neuroendocrine, immune and metabolic functions. Subjects with decreased amounts of fat in their adipose tissue, i.e., lipoatrophy, have low leptin levels. In the context of open-label, uncontrolled studies leptin administration, in physiological replacement doses, has been shown to have metabolically salutary effects in the rare patients with the syndrome of congenital lipodystrophy accompanied by leptin deficiency. Much more patients with lipodystrophy suffer from lipodystrophy and the metabolic syndrome associated with the use of highly active antiretroviral therapy. In this so called highly active antiretroviral therapy (HAART)-associated lipodystrophy and metabolic syndrome, patients demonstrate fat maldistribution with dyslipidemia, insulin resistance, and other metabolic complications. Leptin administration has been shown to decrease central fat mass and to improve fasting insulin/glucose levels and insulin sensitivity in human immunodeficiency virus-infected hypoleptinemic patients with HAART induced lipodystrophy and the metabolic syndrome. By contrast, the results of leptin treatment in leptin replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. In this review, we present the emerging clinical applications and potential therapeutic uses of leptin in humans with lipodystrophy and the metabolic syndrome.
Antiretroviral therapy, highly active; Glucose metabolism; HIV; Leptin; Lipodystrophy
HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest.
A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites.
our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk.
Lipodystrophy is common in patients infected with human immunodeficiency virus receiving highly active antiretroviral therapy, and presents with morphologic changes and metabolic alterations that are associated with depressive behavior and reduced quality of life. We examined the effects of exercise training on morphological changes, lipid profile and quality of life in a woman with human immunodeficiency virus presenting with lipodystrophy.
A 31-year-old Latin-American Caucasian woman infected with human immunodeficiency virus participated in a 12-week progressive resistance exercise training program with an aerobic component. Her weight, height, skinfold thickness, body circumferences, femur and humerus diameter, blood lipid profile, maximal oxygen uptake volume, exercise duration, strength and quality of life were assessed pre-exercise and post-exercise training. After 12 weeks, she exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC) (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high-density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%), exercise duration (37.5%) and strength (65.5%). Quality of life measures improved mainly for psychological and physical measures, independence and social relationships.
These findings suggest that supervised progressive resistance exercise training is a safe and effective treatment for evolving morphologic and metabolic disorders in adults infected with HIV receiving highly active antiretroviral therapy, and improves their quality of life.
Patients with human immunodeficiency virus (HIV) infection are at risk for Mycobacterium tuberculosis (TB) coinfection. The advent of antiretroviral therapy restores immunity in HIV-infected patients, but predisposes patients to immune reconstitution inflammatory syndrome (IRIS).
A 25-year-old HIV-infected male presented with fever, productive cough, and body weight loss for 2 months. His CD4 cell count was 11 cells/μl and HIV-1 viral load was 315,939 copies/ml. Antituberculosis therapy was initiated after the diagnosis of pulmonary TB. One week after antituberculosis therapy, antiretroviral therapy was started. However, multiple mediastinal lymphadenopathies and chylothorax developed. Adequate drainage of the chylothorax, suspension of antiretroviral therapy, and continued antituberculosis therapy resulted in successful treatment and good outcome.
Chylothorax is a rare manifestation of TB-associated IRIS in HIV-infected patients. Careful monitoring for development of IRIS during treatment of HIV-TB coinfection is essential to minimize the associated morbidity and mortality.
We report the case of a 13-year-old boy with bilateral distal femoral unicameral bone cysts (UBCs) associated with acquired generalized lipodystrophy. As opposed to congenital generalized lipodystrophy, cystic bone lesions in acquired generalized lipodystrophy are rare. After radiographic and histologic confirmation of the UBCs, we performed percutaneous intramedullary decompression, curettage, and grafting. UBCs can be an important manifestation of acquired generalized lipodystrophy. Cystic bone lesions appear to be less common in acquired generalized lipodystrophy than in congenital generalized lipodystrophy, and intramedullary adipose tissue loss may be a predisposing factor for the development of bone lesions in patients with acquired generalized lipodystrophy. When evaluating a patient with lipodystrophy, doctors should recognize the clinical course may include the development of UBCs.
Persons with HIV infection develop metabolic abnormalities related to their antiretroviral therapy and HIV infection itself. The objective of this study was to summarize the emerging evidence for the incidence, etiology, health risks, and treatment of dyslipidemias in HIV disease.
Systematic review of original research with quantitative synthesis.
Dyslipidemia is common in persons with HIV infection on highly active antiretroviral therapy (HAART), but methodologic differences between studies preclude precise estimates of prevalence and incidence. The typical pattern includes elevated total cholesterol, low-density lipoprotein cholesterol, and triglycerides, which may be markedly elevated. The dyslipidemia may be associated with lipodystrophy, insulin resistance, and, rarely, frank diabetes mellitus. Exposure to protease inhibitors (PIs) is associated with this entire range of metabolic abnormalities. PI-naïve patients on nucleoside reverse transcriptase inhibitors (NRTIs) may develop lipodystrophy, insulin resistance, hypercholesterolemia, and possibly modest elevations in triglycerides but not severe hypertriglyceridemia, which appears to be linked to PIs alone. Most studies have not found an association between CD4 lymphocyte count or HIV viral load and lipid abnormalities. The pathogenesis is incompletely understood and appears to be multifactorial. There are insufficient data to definitively support an increased coronary heart disease risk in patients with HIV-related dyslipidemia. However, some of the same metabolic abnormalities remain firmly established risk factors in other populations. Patients on HAART with severe hypertriglyceridemia may develop pancreatitis or other manifestations of the chylomicronemia syndrome. Some of the metabolic derangements (particularly hypertriglyceridemia) may improve upon replacing a PI with a non-nucleoside reverse transcriptase inhibitor. The limited experience suggests that fibrates, pravastatin, and atorvastatin can safely treat lipid abnormalities in HIV-infected patients.
Patients with HIV infection on HAART should be screened for lipid disorders, given their incidence, potential for morbidity, and possible long-term cardiovascular risk. Treatment decisions are complex and must include assessments of cardiac risk, HIV infection status, reversibility of the dyslipidemia, and the effectiveness and toxicities of lipid-lowering medications. The multiple potential drug interactions with antiretroviral or other HIV-related medications should be considered in lipid-lowering drug selection and monitoring.
hyperlipidemia; triglycerides; HIV; lipodystrophy; protease inhibitors; HAART
Diabetic mastopathy is the occurrence of lymphocytic mastitis and stromal fibrosis in men as well as women having long-standing diabetes. Clinical and radiological appearance can raise a suspicion of malignancy and result in unnecessary biopsy. As these lesions are known to recur; failure to recognise them can have devastating results. A case of diabetic mastopathy is therefore presented for the knowledge and benefit of all so that unnecessary surgery can be avoided.
Breast cancer; Breast mass; Mastopathy; Diabetic mastopathy; Diabetes mellitus; B-‐lymphocytes; Lymphocytic mastitis
Introduction. Whilst most consequences of diabetes mellitus are well recognized, breast-related complications remain obscure. The term diabetic mastopathy (DMP) attempts to describe the breast-related consequences of diabetes. Methods. We report the clinicopathologic findings in a patient with DMP and review the literature on this uncommon entity. Results. A 33-year-old woman with type 1 diabetes had excision biopsy of a 2 cm breast lump. Histopathologic evaluation revealed classic features of DMP: parenchymal fibrosis; keloid-like hyalinization of interlobular stroma; adipose tissue entrapment; lobular compression; dense chronic inflammatory cell infiltration; and lymphoid follicle formation. Conclusion. Clinicians should be aware of DMP as a differential for breast disease in women with uncontrolled diabetes.
With widespread use of antiretroviral therapy (ART) and prolonged survival of HIV-infected children, toxicities like lipodystrophy are becoming more evident. Little is known about lipodystrophy in children in Uganda yet there is increased use of ART. The aim of this study was to determine the prevalence and factors associated with fat redistribution and metabolic abnormalities among HIV-infected children on highly active antiretroviral therapy (HAART) in Uganda.
A cross-sectional study of 364 HIV positive children aged between 2 and 18 years on ART were enrolled after consent and assent as appropriate. Sociodemographic, clinical and immunological data were collected and recorded in a questionnaire. Fat redistribution was assessed clinically for physical findings of lipohypertrophy and lipoatrophy. A fasting blood sample was taken for lipid profile and blood glucose analysis. Lipodystrophy was defined as presence of abnormal fat redistribution or metabolic abnormalities or both. The proportion of children with fat redistribution and metabolic abnormalities was calculated. We conducted multivariate analysis for factors associated with lipodystrophy among children with lipodystrophic features and those without.
The median age of the participants was eight years (range 2 to 18), with 43% of these aged ≥10 years and a male to female ratio of 1.1:1. Majority (65%) had advanced HIV (WHO Stage III/IV) at ART initiation with a mean duration on ART of 3.8 years (±1.2). The prevalence of fat redistribution and hyperlipidemia was 27.0% and 34.0%, respectively. None of the children had hyperglycaemia. Among the children with hyperlipidemia, 16.8% exhibited hypercholesterolemia and 83% had hypertriglyceridemia. Only 29% of children with fat redistribution had hyperlipidemia. We found significant association between fat redistribution and Tanner stages 2 to 5 OR=2.3 (95%CI 1.3 to 3.8), age≥5 years OR=3.9 (95%CI 1.5 to 9.9) and d4T exposure OR=3.4 (95%CI 2.0 to 5.8). A Tanner stage 2 to 5 was independently associated with hyperlipidemia. No significant association was observed with HIV clinical stage and any of the anthropometric measurements.
The prevalence of lipodystrophy is high among HIV-infected children on ART with a likelihood of developing fat redistribution and metabolic abnormalities increased during puberty.
human immunodeficiency virus; children; lipodystrophy; fat redistribution; hyperlipidemia; metabolic abnormalities; highly active antiretroviral therapy
Diabetic mastopathy is an unusual fibroinflammatory breast lesion that characteristically presents in premenopausal women with long-standing type 1 diabetes mellitus.
Patients present with clinically suspicious breast masses or axillary lymph nodes with imaging characteristics indistinguishable from malignancy. Fine needle aspiration is often inadequate and a core biopsy should be performed. Excisional biopsy is not necessary, and annual follow-up is recommended. Recognition of diabetic mastopathy should lead to better care of patients with breast nodules or axillary masses who are diabetic, avoiding surgery for this benign condition.
Early diagnosis is a tenet in oncology and should enable early treatment with the expectation of improved outcome. Extent and determinants of patient delay of diagnosis in breast cancer patients and its impact on stage of disease were examined in a population based study among female breast cancer patients in Germany. Two hundred and eighty-seven women, aged 18 to 80 years with newly diagnosed invasive symptomatic breast cancer, were interviewed with respect to the diagnostic process. Patient delay was defined as time from onset of first symptoms to first consultation of a doctor. Median patient delay was 16 days among symptomatic patients. Eighteen per cent of all breast cancer patients waited longer than 3 months before consulting a physician. Long patient delay was associated with old age, history of a benign mastopathy, obesity, and indices of health behaviour such as not knowing a gynaecologist for out-patient care and non-participation in general health screening examinations. A strong association between patient delay and stage at diagnosis was observed for poorly differentiated tumours. These results suggest that at risk groups for delaying consultation can be identified and that a substantial proportion of late stage diagnoses of poorly differentiated breast cancer cases could be avoided if all patients with breast cancer symptoms would present to a doctor within 1 month.
British Journal of Cancer (2002) 86, 1034–1040. DOI: 10.1038/sj/bjc/6600209 www.bjcancer.com
© 2002 Cancer Research UK
breast neoplasm; neoplasm staging; socio-demographic factors; health behaviour; diagnostic delay
A case of lymphocytic mastopathy (LM) and concomitant infiltrating lobular breast carcinoma is described. The inflammatory infiltrate cuffed areas of carcinoma. The LM changes also affected lobules that had not been infiltrated by the carcinoma, although adjacent areas contained both in situ and infiltrating tumour. A minor portion of the inflammation was distributed throughout the ducts. The striking lobulocentricity of the inflammatory infiltrate corresponds to previous reports of LM, and distinguishes this case from the inflammatory response commonly associated with breast carcinomas. It is highly likely that the breast carcinoma induced the LM changes in lobules not yet harbouring tumour.
Lipodystrophy is a common long-term complication of HIV infection that may lead to decreased quality of life and less adherence to antiretroviral therapy (ART). A complete understanding of the etiology of HIV-associated lipodystrophy has not as yet been achieved, although factors related to the virus, per se, and use of ART appear to be related. Alcohol use is common among HIV-infected patients and has biological effects on fat distribution, yet alcohol’s relationship to HIV-associated lipodystrophy has not been examined. The goal of this clinical study was to assess the effect of alcohol consumption on lipodystrophy in HIV-infected adults with alcohol problems. This was a prospective study (2001 - 2006) of 289 HIV-infected persons with alcohol problems. The primary outcome was self-reported lipodystrophy, which was assessed at one timepoint (median 29 months after enrollment). Alcohol use was assessed every 6 months and classified as: abstinent at all interviews; ≥1 report of moderate drinking but no heavy drinking; 1 or 2 reports of heavy drinking; or ≥3 reports of heavy drinking. Multivariable logistic regression models were fit to the data. Fifty-two percent (150/289) of subjects reported lipodystrophy. Alcohol consumption was: 34% abstinent at all interviews; 12% ≥1 report of moderate drinking, but no heavy drinking; 34% 1-2 reports of heavy drinking; 20% ≥3 reports of heavy drinking. Although not statistically significant, subjects with alcohol use had a higher odds of lipodystrophy [adjusted odds ratios and 95% CI: ≥1 report of moderate drinking, 2.36 (0.89, 6.24); 1-2 reports of heavy drinking, 1.34 (0.69, 2.60); ≥3 reports of heavy drinking, 2.07 (0.90, 4.73)]. Alcohol use may increase the odds of developing HIV-associated lipodystrophy among subjects with alcohol problems. However, larger studies are needed to elucidate fully the role and impact of alcohol consumption on the development of this common long-term complication of HIV infection and its treatment.
lipodystrophy; HIV; alcohol consumption
The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.
Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.
The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients.
We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively.
The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p < 0.0001 and p < 0.001, respectively). Using the average OARI as the dependent variable, total serum cholesterol level, HDL, triglycerides, glycemia, sex, blood pressure, age and PRFT were independent factors associated with OARI. A PRFT of 6.1 mm was the most discriminatory value for predicting an OARI > 0.74 (sensitivity 78.9%, specificity 82.8%).
Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.
Despite the widely accepted association between crusted scabies and human immunodeficiency virus (HIV)-infection, crusted scabies has not been included in the spectrum of infections associated with immune reconstitution inflammatory syndrome in HIV-infected patients initiating antiretroviral therapy.
We report a case of a 28-year-old Mexican individual with late HIV-infection, who had no apparent skin lesions but soon after initiation of antiretroviral therapy, he developed an aggressive form of crusted scabies with rapid progression of lesions. Severe infestation by Sarcoptes scabiei was confirmed by microscopic examination of the scale and skin biopsy. Due to the atypical presentation of scabies in a patient responding to antiretroviral therapy, preceded by no apparent skin lesions at initiation of antiretroviral therapy, the episode was interpreted for the first time as “unmasking crusted scabies-associated immune reconstitution inflammatory syndrome”.
This case illustrates that when crusted scabies is observed in HIV-infected patients responding to antiretroviral therapy, it might as well be considered as a possible manifestation of immune reconstitution inflammatory syndrome. Patient context should be considered for adequate diagnosis and treatment of conditions exacerbated by antiretroviral therapy-induced immune reconstitution.
Crusted scabies; IRIS; HIV; AIDS; ART
On rare occasions, patients infected with human immunodeficiency virus (HIV) can develop a disorder similar to chronic progressive external ophthalmoplegia (CPEO) while undergoing long-term treatment with antiretroviral therapy. Orbital imaging may help explain the pathogenesis of this abnormality.
In this case series, 5 adult patients who presented with a CPEO-like disorder after more than 10 years of antiretroviral therapy and who underwent T1-weighted high-resolution magnetic resonance imaging (MRI) of the orbits and brain were retrospectively identified. Patients also were screened for acetylcholine receptor antibody levels.
All patients had bilateral external ophthalmoplegia and blepharoptosis. Acetylcholine receptor antibody titers were not increased. Brain MRI was unremarkable. Orbital MRI showed patchy bright signal inside the extraocular muscles that had conserved volume.
Patients with HIV under long-term antiretroviral therapy may develop functional abnormalities of extraocular muscles that are structurally normal in size, that is, changes are similar to those observed in the orbital MRIs of patients with CPEO. This constellation of signs and symptoms suggests a possible role of HIV disease or antiretroviral therapy in the CPEO-like syndrome observed in some HIV-infected individuals.
There is a significant prevalence (20%–80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment–associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed.
HIV; Lipodystrophy; Dyslipidemia; Statin therapy; Cardiovascular risk prevention; Review
The classic kidney disease of Human Immunodeficiency Virus (HIV) infection, HIV-associated nephropathy, is characterized by progressive acute renal failure, often accompanied by proteinuria and ultrasound findings of enlarged, echogenic kidneys. Definitive diagnosis requires kidney biopsy, which demonstrates collapsing focal segmental glomerulosclerosis with associated microcystic tubular dilatation and interstitial inflammation. Podocyte proliferation is a hallmark of HIV-associated nephropathy, although this classic pathology is observed less frequently in antiretroviral-treated patients. The pathogenesis of HIV-associated nephropathy involves direct HIV infection of renal epithelial cells, and the widespread introduction of combination antiretroviral therapy has had a significant impact on the natural history and epidemiology of this unique disease. These observations have established antiretroviral therapy as the cornerstone of treatment for HIV-associated nephropathy, in the absence of prospective clinical trials. Adjunctive therapy for HIV-associated nephropathy includes ACE inhibitors or angiotensin receptor blockers, as well as corticosteroids in selected patients with significant interstitial inflammation or rapid progression.
HIV-associated nephropathy; focal segmental glomerulosclerosis; HIV; kidney
Combined antiretroviral therapy (cART) in the treatment of HIV-1 infection has been associated with complications, including lipodystrophy, hyperlipidaemia, insulin resistance (IR) and diabetes.
To compare the prevalence of glucose homeostasis disturbances and IR in HIV patients on cART according to the presence of lipodystrophy (defined clinically and by Fat Mass Ratio) and different patterns of fat distribution and to establish their associations.
Cross-sectional cohort study.
We evaluated body composition and IR and insulin sensitivity indexes in 345 HIV-infected adults.
Patients with clinical lipodystrophy (CL) had higher plasma glucose levels than patients without CL, without significant differences in plasma insulin levels, A1c, HOMA-IR, HOMA-B, QUICKI, or MATSUDA index. Patients with lipodystrophy defined by FMR had higher plasma glucose and insulin levels, A1c, HOMA-IR, QUICKI and MATSUDA than patients without lipodystrophy, without differences in HOMA-B. Higher insulin resistance (HOMA-IR ≥ 4) was present in patients with FMR-defined lipodystrophy. Patients with FMR-defined lipodystrophy had a higher prevalence of IFG, IGT and DM than patients without lipodystrophy. Significant associations between HOMA-IR and total, central and central/peripheral fat evaluated by CT at abdominal level were found and no association between HOMA-IR and peripheral fat. Association between HOMA-IR and total and trunk fat but no association with leg and arm fat (evaluated by DXA) was found.
IR and glucose disturbances were significantly increased in patients with FMR-defined lipodystrophy. FMR lipodystrophy definition seems to be a more sensitive determinant of insulin resistance and glucose disturbances than clinical definition.
Lipodystrophy; Insulin resistance; HIV; Glucose homeostasis disturbances
Coinfection with hepatitis B virus (HBV) is not uncommon in human immunodeficiency virus (HIV)-infected individuals and patients with HIV-HBV coinfection are at high risk for progression of liver disease. Current guidelines regarding the treatment of HIV infection recommend that patients who are coinfected with HIV and HBV receive highly active antiretroviral therapy (HAART) with activity against hepatitis B. While HIV-HBV coinfected patients often experience liver enzyme elevations after starting antiretroviral therapy, acute liver failure (ALF) is rare and typically occurs with older antiretroviral agents with known potential for hepatotoxicity. We describe two cases of fatal ALF in the setting of HIV-HBV coinfection after initiation of HAART. These cases occurred despite treatment with antiretrovirals that have activity against HBV and highlight the challenges in distinguishing drug hepatotoxicity and HBV immune reconstitution inflammatory syndrome. HIV-HBV coinfected patients should be monitored closely when initiating HAART, even when treatment includes agents that have activity against HBV.
Hepatitis B virus; Human immunodeficiency virus; Liver failure