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Acquired Immunodeficiency Syndrome

Acquired Immune Deficiency Syndrome

Acquired immunodeficiency syndrome (AIDS) is considered to be the most severe stage of human immunodeficiency virus (HIV) infection. It is life-threatening if therapy is not initiated immediately. Patients present with constitutional symptoms of variable severity, wasting, and numerous AIDS-defining illnesses. Clinical and laboratory criteria, especially a very low CD4+T-cell count, are used to make the diagnosis.


Presentation

AIDS occurs in patients who suffer from a severe and long unrecognized human immunodeficiency virus (HIV) infection (caused by either HIV-1 or HIV-2 virus) [1] [2] [3]. AIDS is almost never encountered in patients with an acute HIV infection, but rather develops after the period of latency and progressive decrease in CD4+T-cell function [4] [5]. One of the most important risk factors is the lack of treatment, mostly because of a missed (or unknown) diagnosis. The progressive nature of HIV infection symptoms and infections have been grouped into two diagnostic criteria devised by the Center for Disease Control (CDC) and the World Health Organization (WHO). As per CDC criteria, three distinct categories exist - A, B, and C, with A describing features of acute or asymptomatic HIV infection [2] [6]. On the other hand, categories B and C (similarly to clinical stages 2,3 and 4 of WHO criteria) include the appearance of AIDS-related conditions. Constitutional symptoms such as fever, fatigue, or diarrhea lasting for at least one month, peripheral neuropathy and numerous infections - Listeriosis, Bacillary angiomatosis, recurrent herpes zoster involving > 1 dermatome and pelvic inflammatory disease (PID) are initial signs of AIDS [1] [2] [3] [6] [7]. Candidiasis, however, is the most important group B feature of patients with suspected HIV or AIDS and can present in the oropharynx or the genitalia. Additional disorders that belong to the B category are immune thrombocytopenic purpura (ITP), cervical dysplasia (or cervical carcinoma in situ) and oral hairy leukoplakia. When patients present with profound weight loss and poor general condition due to "wasting syndrome" caused by HIV, they are adequately classified into category C and clinical stage 4, respectively, and signs of severe AIDS include [1] [2] [3] [6] [7]:

Generalized Lymphadenopathy
  • Editorial Note Editorial Note: The report above documents the occurrence of cases of unexplained, persistent, generalized lymphadenopathy among homosexual males.[cdc.gov]
  • Persistent, generalized lymphadenopathy among homosexual males. MMWR 1982;31:249-51. CDC. Diffuse, undifferentiated non-Hodgkins lymphoma among homosexual males--United States. MMWR 1982;31:277-9.[cdc.gov]
  • Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea.[icd9data.com]
  • The standard surveillance definition of AIDS does not apply to suspected subclinical or mild cases of AIDS--to the extent they occur--or to cases involving persistent generalized lymphadenopathy or other conditions in persons from high-risk groups.[cdc.gov]
Fever
  • Pneumocystis carinii and fever improved immediately when ST mixture and highly active antiretroviral therapy (HAART) were performed.[ncbi.nlm.nih.gov]
  • Abstract A 33-year-old male presented with a history of fever and cough and was diagnosed to have pulmonary tuberculosis and acquired immunodeficiency syndrome (AIDS).[ncbi.nlm.nih.gov]
  • Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass.[ncbi.nlm.nih.gov]
  • The authors present a rare case of primary psoas abscess in patient affected by acquired human immunodeficiency syndrome, showing a mass in the inferior lumbar region through the lumbar triangle of Petit and fever.[ncbi.nlm.nih.gov]
  • Surprisingly, fever resolved almost immediately, in parallel with dramatic decreases in serum levels of ferritin and liver enzymes and prompt normalization of coagulopathy with only two doses of rTM.[ncbi.nlm.nih.gov]
Candidiasis
  • Abstract Disseminated cryptococcosis and recurrent oral candidiasis was presented in a-heterosexual AIDS patient.[ncbi.nlm.nih.gov]
  • Infectious diseases comprised of TB; 4 cases, cytomegalovirus infection (CMV) 4; bacterial pneumonia and meningitis; 7, and esophageal candidiasis in 2 cases.[ncbi.nlm.nih.gov]
  • ., tuberculosis, oral candidiasis, herpes zoster) to malignant neoplasms that cause, as well as result from, immunodeficiency((P)) (5).[cdc.gov]
  • In April 1982, he developed fever and oral candidiasis, and began to lose weight.[cdc.gov]
  • Candidiasis, however, is the most important group B feature of patients with suspected HIV or AIDS and can present in the oropharynx or the genitalia.[symptoma.com]
Weight Loss
  • Here, I report the case of a 31-year-old immigrant Burmese woman who exhibited epigastralgia, fever, weight loss and an epigastric mass.[ncbi.nlm.nih.gov]
  • The case of a 41-year-old male with AIDS who presented with weight loss, abdominal pain, ascites, edema, nausea, vomiting, and diarrhea is discussed. A computed tomography (CT) scan of the abdomen showed avid enhancement of the stomach mucosa.[ncbi.nlm.nih.gov]
  • loss, lymphadenopathy, and the occurrence of opportunistic infections and malignant tumours; abbreviated AIDS.[oxforddictionaries.com]
  • The first symptoms of the illness are generally night sweats, weight loss, and oral thrush.[conservapedia.com]
  • When patients present with profound weight loss and poor general condition due to "wasting syndrome" caused by HIV, they are adequately classified into category C and clinical stage 4, respectively, and signs of severe AIDS include: Infections - Candidiasis[symptoma.com]
Fatigue
  • Fatigue was defined by patient self-report. The outcomes were the prevalence of fatigue and the potential risk factors of fatigue.[ncbi.nlm.nih.gov]
  • Constitutional symptoms such as fever, fatigue, or diarrhea lasting for at least one month, peripheral neuropathy and numerous infections - Listeriosis, Bacillary angiomatosis, recurrent herpes zoster involving 1 dermatome and pelvic inflammatory disease[symptoma.com]
  • Symptoms may include night sweats and fatigue, fever, cough, difficulty breathing, weight loss. Most likely to occur when the CD4 T cell count falls below 200.[conservapedia.com]
  • Eight months later, the donor complained of fatigue and decreased appetite. On examination, he had right axillary lymphadenopathy, and cotton-wool spots were seen in the retina of the left eye.[cdc.gov]
  • These may include dyspnea, nutritional wasting, fatigue, pain, and incontinence.[medical-dictionary.thefreedictionary.com]
Anemia
  • In univariate analysis, the significant differences in demographic characteristics between patients with and without fatigue were: gender [OR 2.29; 95% CI (1.05-4.98)], education level [OR 0.40; 95% CI (0.18-0.85)], anemia [OR 3.80; 95% CI (1.27-11.31[ncbi.nlm.nih.gov]
  • Moyamoya syndrome is associated with meningitis, tuberculosis, syphilis, head trauma, head irradiation, brain tumor, von Recklinghausen's disease, tuberous sclerosis, Marfan syndrome, sickle cell anemia, arteriosclerosis, hypertension, and oral contraceptive[ncbi.nlm.nih.gov]
  • At 14 months of age, the infant developed neutropenia and an autoimmune hemolytic anemia and thrombocytopenia.[cdc.gov]
  • Chronic physical problems like anemia, infections of the urinary tract, incontinence, infertility, pain, menstruation problems and dyspareunia are frequent. Women also have a higher risk for HIV infections.[dx.doi.org]
  • Bacterial infection that can cause persistent fever, night sweats, fatigue, weight loss, anemia, abdominal pain, dizziness, diarrhea and weakness. Most likely occurs when the CD4 T cell count falls below 50. Mycobacterium tuberculosis (TB).[conservapedia.com]
Cough
  • Abstract A 33-year-old male presented with a history of fever and cough and was diagnosed to have pulmonary tuberculosis and acquired immunodeficiency syndrome (AIDS).[ncbi.nlm.nih.gov]
  • This is the case of a patient with multiple secondary sexually transmitted infectious diseases, lymphadenopathy, B-cell lymphoma, a productive cough, a clinical picture suggestive of pulmonary tuberculosis, eosinophilia, and a new-onset acquired immunodeficiency[ncbi.nlm.nih.gov]
  • .  Coughing or sneezing Sharing cups, plates and other eating utensils Sharing water or food Handshakes, touching or hugging Using the same toilet Insect bites 6. Sore throatFeverNight sweatingFatigueColdNausea 7.[slideshare.net]
  • Pertussis, also known as whooping cough, is a highly contagious respiratory disease. It is caused by the bacterium Bordetella pertussis . Pertussis is known for uncontrollable, violent coughing that often makes it hard to breathe.[niaid.nih.gov]
  • When people with lung TB cough, sneeze or spit, they propel the TB germs into the air. A person needs to inhale only a few of these germs to become infected.[who.int]
Chronic Cough
  • There may be a chronic cough with crepitations in both lungs. Hepatomegaly and splenomegaly may be detected in the abdomen. In infants, crusting around the anus may be a sign of chronic diarrhoea.[patient.info]
Diarrhea
  • The case of a 41-year-old male with AIDS who presented with weight loss, abdominal pain, ascites, edema, nausea, vomiting, and diarrhea is discussed. A computed tomography (CT) scan of the abdomen showed avid enhancement of the stomach mucosa.[ncbi.nlm.nih.gov]
  • Keywords: non-human primate, chronic diarrhea, aids, hiv, siv Abstract: Diarrhea is the pathophysiological reaction of hosts gastrointestinal tract to a variety of external stimuli.[doi.org]
  • Diarrhea is the pathophysiological reaction of host's gastrointestinal tract to a variety of external stimuli. Classified as a clinical syndrome, diarrhea is the leading cause of mortality and morbidity worldwide.[ncbi.nlm.nih.gov]
  • Constitutional symptoms such as fever, fatigue, or diarrhea lasting for at least one month, peripheral neuropathy and numerous infections - Listeriosis, Bacillary angiomatosis, recurrent herpes zoster involving 1 dermatome and pelvic inflammatory disease[symptoma.com]
  • Common presentations include headache, fits, altered mental status, or paralysis Cryptosporidium diarrhea, which is marked by the presence of extreme watery-diarrhea and caused by the parasite Cryptosporidium.[dovemed.com]
Chronic Diarrhea
  • Because of its impact on the host immune system, acquired immune deficiency syndrome (AIDS) is currently the major cause of chronic diarrhea in many parts of the world.[doi.org]
  • Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea.[icd9data.com]
  • diarrhea (over 1 month), diagnosed by histology or stool microscopy; (3) bronchial or pulmonary candidiasis, diagnosed by microscopy or by presence of characteristic white plaques grossly on the bronchial mucosa (not by culture alone); (4) non-Hodgkin's[cdc.gov]
  • The patient had a history of chronic diarrhea, progressive dyspnea and loss of approximately 20kg in eight months. Seven days prior to admission, he began a progressive decrease in consciousness.[scielo.br]
Failure to Thrive
  • The clinical manifestations were failure to thrive; 9 children, persistent gastroenteritis; 8, recurrent fever; 5, bacterial infections; 5, hepatosplenomegaly; 5, candidiasis; 1, scabies; 1, skin rash; 2, tuberculous (TB) meningitis; 1 and paraplegia;[ncbi.nlm.nih.gov]
  • Testing can be done within the first few months, but it is also important to recognize the early signs: recurrent infections and failure to thrive.[healthline.com]
  • Common gastrointestinal symptoms include diarrhoea, malabsorption and failure to thrive or losing weight.[patient.info]
  • […] to thrive ( B20 ) physical retardation due to malnutrition ( E45 ) ICD-10-CM Diagnosis Code R75 Inconclusive laboratory evidence of human immunodeficiency virus [HIV] 2016 2017 2018 2019 Billable/Specific Code Applicable To Nonconclusive HIV-test finding[icd10data.com]
  • As the disease progresses, characteristics are a general failure to thrive, anergy, and any of a variety of recurring infections, most commonly Pneumocystis pneumonia, tuberculosis, meningitis, and encephalitis caused by aspergillosis, candidiasis, cryptococcosis[medical-dictionary.thefreedictionary.com]
Loss of Appetite
  • Several symptoms, such as weight loss and loss of appetite, were more common in our subjects with PHI.[aidsonline.com]
  • […] of appetite, leading to a disproportionate loss of strength in different muscles in the body The CD4 lymphocyte count predicts the type of opportunistic infections and cancers an HIV-infected individual can develop as the count decreases Sometimes, an[dovemed.com]
  • Eight months after the incident, the worker reported low-grade fever, chills, myalgia, nausea, vomiting, diarrhea, sweating, headache, and loss of appetite.[content.nejm.org]
  • An overgrowth of yeast causes white patches on gums, tongue or lining of the mouth, pain, difficulty in swallowing and loss of appetite. Candida in the esophagus, trachea, bronchi or lungs is AIDS defining.[ucsfhealth.org]
  • The resultant chronic disease state is associated with inflammatory responses which can lead to further weight loss due to loss of appetite, malabsorption, and development of specific nutrient deficiencies and imbalances ( de Pee 2010 ).[doi.org]
Perianal Ulcer
  • Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med 1981;305:1439-44. Marmor M, Friedman-Kien AE, Laubenstein L., et al.[cdc.gov]
  • Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med. 1981;305(24):1439–44. PubMed Google Scholar 14.[springerlink.com]
  • ulcerative herpes simplex lesions.[doi.org]
Social Isolation
  • This includes having regular dental checks and their own accommodation. [ 19 ] There may be an element of social isolation and psychological issues may need to be addressed.[patient.info]
  • Unemployment in people with HIV/AIDS also is associated with suicidal ideation, memory problems, and social isolation. Employment increases self-esteem, sense of dignity, confidence, and quality of life for people with HIV/AIDS.[en.wikipedia.org]
  • Direct mechanisms are those that increase the likelihood of a person coming into contact with someone who is HIV positive, for example, through residential segregation and the social isolation of marginalized populations.[epirev.oxfordjournals.org]
  • Generally, frequent or long‐term absence from work leads to job loss and may result in depression, financial insecurity, and social isolation ( Henderson 2005 ; Linn 1985 ).[doi.org]
Peripheral Neuropathy
  • Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy.[doi.org]
  • Abstract Peripheral neuropathy is the most common neurological complication in HIV and is often associated with antiretroviral therapy.[ncbi.nlm.nih.gov]
  • Constitutional symptoms such as fever, fatigue, or diarrhea lasting for at least one month, peripheral neuropathy and numerous infections - Listeriosis, Bacillary angiomatosis, recurrent herpes zoster involving 1 dermatome and pelvic inflammatory disease[symptoma.com]
  • Qiankunning appeared not to affect HIV-1 RNA levels (Shi 2003), Curcumin ineffective in reducing viral load or improving CD4 cell counts (Hellinger 1996), and Capsaicin ineffective in relieving pain associated with HIV-related peripheral neuropathy (Paice[ncbi.nlm.nih.gov]
Sexual Dysfunction
  • ''And we never find out about sexual dysfunction or about a grandparent who is afraid to touch his grandchild or about a patient who has to sit alone at family gatherings because everyone is afraid he'll give them AIDS.''[nytimes.com]

Workup

Because many disorders are a part of the clinical presentation of AIDS, physicians must maintain a high index of suspicion when any of the mentioned illnesses or infections appear together with a poor general condition. For this reason, a comprehensive workup is necessary to rule out HIV infection and AIDS as a possible cause [2]. Firstly, a detailed patient history must include assessment of potential risk factors such as unprotected sexual intercourse, particularly male homosexual (as the vast majority of patients in the developed world are males belonging to the men having sex with men - MSM population), contact with blood products (through intravenous drug use) or a positive family history in the setting of vertical transmission [2] [6] [7]. Moreover, the appearance of any of the infections (or their respective signs and symptoms) in recent months should be noted, and a detailed and complete physical examination may confirm cutaneous, pulmonary, or general manifestations of AIDS and warrant a laboratory investigation to diagnose the clinical entity. A neurological exam (including the mini-mental status examination) must be carried out in all patients suspected to have severe HIV infection, in order to assess the extent of neurological involvement and detect AIDS-related dementia. In addition to a complete blood count (CBC), which will show lymphopenia in virtually all patients, an extensive biochemical panel is necessary to evaluate organ status - lipid profile, liver and kidney function, and a full electrolyte panel [2] [3] [7]. If the diagnosis of HIV is not already known, testing for HIV antibodies is the first step in confirming this infection, followed by a CD4+T-cell count and isolation of viral RNA through polymerase chain reaction (PCR) analysis. Classification of patients harboring an HIV infection, supplementary to clinical criteria, is based on the CD4+T-cell count as well, and a number of < 200/µL is diagnostic for AIDS [2]. Additional recommended procedures include syphilis testing with the Venereal disease research laboratory test (VDRL) and rapid plasma reagin (RPR) tests, detection of anti-toxoplasma antibodies, purified protein derivative (PPD) test for tuberculosis, and determine possible coinfection by hepatitis viruses (A, B, or C) [3] [6] [7].

Anergy
  • Moreover, the findings of anergy and depressed T-lymphocyte helper-to-suppressor ratios in some of the patients with lymphadenopathy suggest cellular immune dysfunction. Patients with KS/OI have had severe abnormalities of cellular immunity (5,6).[cdc.gov]
  • High risk of active tuberculosis in HIV infected drug users with cutaneous anergy. JAMA 1992;268:504-9. Braun MM, Badi N, Ryder R, et al.[cdc.gov]
  • As the disease progresses, characteristics are a general failure to thrive, anergy, and any of a variety of recurring infections, most commonly Pneumocystis pneumonia, tuberculosis, meningitis, and encephalitis caused by aspergillosis, candidiasis, cryptococcosis[medical-dictionary.thefreedictionary.com]
  • The frequency of anergy is not increased during pregnancy, and routine anergy testing for HIV-1--infected pregnant women is not recommended ( 207--210 ).[cdc.gov]
Lymphocytopenia
  • CD4 lymphocytopenia among injecting drug users in New York City. J Acquir Immune Defic Syndr. 1993;6(7):820–2. PubMed Google Scholar 83. Donegan E, Stuart M, Niland JC, et al.[springerlink.com]
Abnormal Renal Function
  • The dose must be adjusted for abnormal renal function. Multiple randomized clinical trials indicate that TMP-SMX is as effective as parenteral pentamidine and more effective than other regimens .[cdc.gov]

Treatment

  • After adjusting for other factors, a shorter time of treatment with TCM, male sex, older age, lower CD4 T-cell counts, and long-term treatment with cART were risk factors of mortality.[ncbi.nlm.nih.gov]
  • […] for treatment of AIDS.[ncbi.nlm.nih.gov]
  • Family's denial of infection as well as 'hiding information' concerning patient's health from physicians involved in her treatment caused a delay in proper on-time patient treatment.[ncbi.nlm.nih.gov]
  • In Africa antiretroviral treatment coverage has increased significantly. This has partly been due to the Treatment 2015 initiative which aims to ensure that the world reaches its 2015 HIV treatment target of 15 million.[patient.info]

Prognosis

  • When patients with penicilliosis/AIDS were diagnosed early and treated with standardized antifungal therapy and combined antiretroviral therapy, their prognosis improved.[ncbi.nlm.nih.gov]
  • Physicians should pay attention to this rare case of progressive outer retinal necrosis associated occlusive vasculitis with very poor prognosis in spite of aggressive treatment. Copyright 2015. Published by Elsevier B.V.[ncbi.nlm.nih.gov]
  • Critical issues surrounding the diagnosis, screening of blood products, treatment of complicating infections and cancers, and prognosis for immunologic recovery in affected persons are unresolved.[annals.org]
  • The high mortality and grim ultimate prognosis seen may have implications for pediatricians attempting to identify the proper limits of medical intervention for this group of patients. respiratory failure acquired immunodeficiency syndrome Pneumocystis[pediatrics.aappublications.org]

Etiology

  • Abstract Ménétrier disease is a rare disorder of unknown etiology. An overexpression of TGF-alpha has been proposed to play a role in the pathophysiology.[ncbi.nlm.nih.gov]
  • If the target cell of AIDS is the mature T cell as suspected, the methods used in these studies may prove useful for the long-term growth of these cells and for the identification of antigens specific for the etiological agent of AIDS.[ncbi.nlm.nih.gov]
  • A second hospitalization, beginning in June 1982, was complicated by Salmonella sepsis, perianal herpes simplex virus infection, encephalitis of unknown etiology, and disseminated cytomegalovirus infection. He died in August 1982.[cdc.gov]
  • This study was undertaken to determine the etiology of acute respiratory failure and the outcome of children with AIDS and AIDS-related complex.[pediatrics.aappublications.org]

Epidemiology

  • This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients.[ncbi.nlm.nih.gov]
  • A historical framework for social epidemiology. In: Berkman LF, Kawachi I, eds. Social epidemiology. New York, NY: Oxford University Press, 2000:3–12. 2. Krieger N. A glossary for social epidemiology.[epirev.oxfordjournals.org]
  • In the absence of direct epidemiological evidence, molecular evolutionary studies of primate lentiviruses provide the most definitive information about the origins of human immunodeficiency virus (HIV)-1 and HIV-2.[ncbi.nlm.nih.gov]
  • Abstract In the absence of direct epidemiological evidence, molecular evolutionary studies of primate lentiviruses provide the most definitive information about the origins of human immunodeficiency virus (HIV)–1 and HIV–2.[dx.doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Currently suggested pathophysiological mechanisms of the disease are mostly derived from stroke cases. Although rare, cerebral toxoplasmosis may strengthen the pathophysiologic mechanism of disease.[ncbi.nlm.nih.gov]
  • An overexpression of TGF-alpha has been proposed to play a role in the pathophysiology. HIV-1 tat gene product has been shown to stimulate TGF-alpha production leading to a positive feedback autocrine loop.[ncbi.nlm.nih.gov]
  • Keywords: non-human primate, chronic diarrhea, aids, hiv, siv Abstract: Diarrhea is the pathophysiological reaction of hosts gastrointestinal tract to a variety of external stimuli.[doi.org]
  • Diarrhea is the pathophysiological reaction of host's gastrointestinal tract to a variety of external stimuli. Classified as a clinical syndrome, diarrhea is the leading cause of mortality and morbidity worldwide.[ncbi.nlm.nih.gov]
  • AIDS Pathophysiology AIDS Transmission AIDS Treatment AIDS Prognosis History of AIDS[news-medical.net]

Prevention

  • […] important strand of AIDS prevention programmes.[patient.info]
  • All the biological prevention strategies depend on behavioural adherence to the given prevention tool, and can be undermined by human rights violations and gender-power imbalances that conspire to reduce access to prevention services.[oxfordmedicine.com]
  • […] infections and prevention of mother-to-child transmission.[scielosp.org]
  • Abstract Varicella zoster virus (VZV) immunization aids in the prevention of future VZV infections in immunocompetent patients; however, severely immunocompromised patients remain at increased risk of VZV infection.[ncbi.nlm.nih.gov]

References

Article

  1. Campbell-Yesufu OT, Gandhi RT. Update on Human Immunodeficiency Virus (HIV)-2 Infection. Clin Infect Dis. 2011;52(6):780-787.
  2. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  3. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  4. Ortblad KF, Lozano R, Murray CJL. The burden of HIV: insights from the Global Burden of Disease Study 2010. AIDS (London, England). 2013;27(13):2003-2017.
  5. GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV. 2016 Aug; 3(8):e361–e387.
  6. Centers for Disease Control and Prevention (CDC). Revised surveillance case definition for HIV infection--United States, 2014. MMWR Recomm Rep. 2014;63(RR-03):1-10.
  7. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.

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Last updated: 2018-06-21 17:43