Main syndromes

A compilation of the main syndromes in medical practice.
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Ider Cerutti, Alejandro B. Miroli

Immune deficiency is manifested by different signs and symptoms associated with the failure of immunity.

Primary or congenital immunodeficiencies are distinguished, and secondary or acquired ones. Primary immunodeficiencies are divided into: a) specific: inability to manifest the humoral or cellular response or both, and b) nonspecific: disorders of phagocytosis or bacteriolosis. And the secondary ones, in turn, in: a) specific: decrease in immune response or immunoglobulins, and b) nonspecific: decrease in phagocytosis associated with neutropenia or pancytopenia.

  1.  Cellular immunity deficiency
    • Thymic Aplasia or Di George Syndrome
    • Nezelof syndrome
  2. Inosine phosphorylase deficiency
    1. Humoral immunity deficiency
    2. Agammaglobulinemia linked to absence of B lymphocytes
    3. Transient hypogammaglobulinemia
    4. Hypogammaglobulinemia of variable expression
    5. Selective IgA deficiency
    6. Selective IgM deficiency
    7. IgG deficiency, IgA with normal IgM
  3. Mixed and severe deficiencies
  4. Complex deficiencies
    1. Immune deficiency and telangiectatic ataxia
    2. Wiscott-Aldrich syndrome
  5. Other immunodeficiencies
  6. Phagocyte immunodeficiency

Chemical aplasia or Di George syndrome . It is characterized by abnormalities in the development of the thymus associated with hypoparathyroidism and congenital malformations.

Nezelof syndrome. Qualitative and quantitative defect of the dependent T functions.

Inosine phosphorylase deficiency. Disorder of purine metabolism manifested in T and B lymphocytes.

Agamma globulinemia linked to the absence of B lymphocytes Also called Burton's disease, it is a recessive genetic process linked to sex that is manifested by a quantitative defect of B lymphocytes.

Transient hypogammaglobilinemia . It persists from birth for several years. It differs from Burton's disease because there is a normal amount of IgM and the presence of B lymphocytes.

Hypogammaglobulinemia of variable expression . It is characterized by qualitative abnormalities of immunity with partial or dissociated compromise of humoral and cellular immunity.

Selective IgA deficiency . Serum IgA rate less than 50 mg / L with normal amounts of IgG and IgM.

Selective IgM deficiency . The deficiency is limited to IgM, since T functions appear to be conserved.

Mixed and serious deficiencies . They are inherited conditions that are manifested in the first months of life by serious infections. The immunological study reveals the global or dissociated deficiency of immunoglobulins, absence of antibody production, inscostant lymphopenia with absence of T lymphocytes, variable presence of B lymphocytes, and a constant and variable deficit of cellular immunity.

Immune deficiency and ataxia telangiectasia . Genetic disease manifested by cerebral ataxia, ocular telangiectasias, and immune deficiencies.

Wiscott-Aldrick syndrome . Association of mixed and partial immune deficiency, thrombocytopenia and chronic eczema.

Other immunodeficiencies. Mixed expression deficiencies associated with short limbs and dwarfism or chronic cutaneumucosal candidiasis have been described. There are also congenital complement deficiencies.

Phagocyte immunodeficiency.Chronic granulomatous disease is a childhood disease determined by the lack of surface oxidase in polymorphonuclear granulocytes, as a consequence of which the phagocytes are unable to generate the superoxide ion. Children with this defect cannot efficiently destroy catalase-positive bacteria such as Staphylococus aureus. Another defect similar to this, but that acts at a different point in the chain of chemical phenomena that lead to intracellular oxidative death, is myeloperoxidase deficiency. Patients form normal amounts of hydrogen peroxide but lack the enzyme myeloperoxidase necessary for the generation of hypochlorite. In Chediak-Higashi disease, part of the defect is due to the inability of the lysosomal granules to discharge hydrolytic enzymes.

Physiopathology

It is families of lymphocytes that develop specific adaptive immune responses which are functionally interactive.

Cellular immunity is mediated by T lymphocytes, and B lymphocytes and plasma cell progeny develop the antibodies that ensure humoral immunity. Dendritic cells, Langerhans cells of the skin and macrophages also play an important role as cells of the Reticulum Endothelial System, which is integrated into lymphocytes. Natural Killers (NK) cells are granular lymphocytes that have specific receptors for the major histocompatibility complexes. Known as Class I Molecules, they can act spontaneously by killing tumor cells or cells infected by viruses. IgG type antibodies can also be stimulated for which it has receptors on its surface.

The immune response is divided into humoral (antibody) and cellular (late immunity). The first involves the interaction of antigens and antibodies; the second, the interaction between antigens and specialized lymphocytes, which act directly and through the elaboration of substances that are not antibodies. Another part of the process is constituted by the intervention of monocytes-macrophages, polymorphonuclear granulocytes and an amplifying system composed of complement, the kinin system and the coagulation-fibrinolysis system, which is basically nonspecific.

Primary impairments are genetically determined, and the time at which clinical manifestations begin varies depending on the nature of the immune defect and the type of exposure to the infectious agent. Carriers with insufficient T and B lymphocytes develop viral and bacterial infections shortly after birth.

In B insufficiency, manifestations appear when the level of IgG transferred by the mother to the fetus transplacentally falls. In general, infections that appear before 6 months suggest a cellular defect; those that appear later, a humoral defect.

And patients with a defective humoral immunity are prone to recurrent or chronic infections, meningitis, and septicemia. Otitis media, pansinusitis, and, less frequently, skin and urinary infections are also reported. People with impaired cellular immunity are predisposed to disseminated viral infections and almost invariably present with candidiasis and diffuse mycosis. Sometimes the only manifestation is a chronic mucocutaneous candidiasis, intestinal giardiasis is also frequent.

T insufficiency is associated with abnormalities in the antibody response, which explains the extent of bacterial infections. The most serious form of deficiency appears in those who lack humoral and cellular immunity, which makes them susceptible to all microorganisms, even non-pathogens. In them, the simultaneous presence of bacterial, viral, and fungal infections is frequent.

Recurrent staphylococcal infections with granuloma formation suggest chronic granulomatous disease. Gram-positive infections are associated with antibody and complement defects.

In the physical examination of these patients, special attention should be paid to the study of the lymph nodes and the organs that have lymphoid and reticuloendothelial tissue. Lymph nodes, tonsils, and adenoids are enlarged when there is a defect in the conversion of B cells to immunoglobulin-secreting plasma cells. They are generally smaller in humoral and cellular insufficiencies. The spleen is absent in congenital aplasia and enlarged in cellular and humoral insufficiencies; Compensatory hepatomegaly may exist as the liver is a reticuloendothelial organ.

Study methodology

  1. Complete clinical history with correct documentation of the disease, age of onset, type and evolution of each infectious episode. Family history of immunodeficiency or recurrent infections. History of homosexuality, hemodialysis, emofilia, multiple transfusions, intravenous drug addiction, contact with a population at risk for AIDS.
  2. Comprehensive physical examination for infectious foci and palpation of lymph nodes, liver and spleen.
  3. Complete clinical laboratory with functional evolution of liver and kidney. Anti-HIV (human immunodeficiency virus)
  4. Hemogram by a hematologist to search for numerical and morphological alterations of white blood cells
  5. Qualitative and quantitative immunoglobulin doping
  6. Chest X-ray for investigation of infectious foci and assessment of the thymus.
  7. Only in isolated cases will studies of the lymphocyte population and functionality of neutrophils and macrophages be requested. Detection of antigens and antibodies.
Table 2: Secondary Inumodeficiencies
Factor Commitment
Age  
Newborns (especially premature) B and T cells, phagocytic system, complement (severe bacterial and viral infections)
Lack of breastfeeding IgA (decreased mucosal protection in the intestine, increased frequency of respiratory and gastrointestinal infections)
Seniors B and T cells (anergy, autoimmunity)
Immunosuppressive treatment  
Corticosteroids B and T cells, phagocytic system (decreased neutrophil chemotaxis)
Antineoplastics and immunosuppressants B and T cells
Ionizing radiation T cells, phagocytic system (decreased number of neutrophils)
Diseases that affect the lymphoid system  
Hodgkin's disease T cells
Non-Hodgkin's Lymphoma, Chronic Lymphatic Leukemia B and T cells
Multiple myeloma B cells (monoclonal peak in serum electrophoresis)
Timoma B cells (hypogammagloblulinemia)
Surgical or functional splenectomy Phagocytic system (decreased clearance of bacteria by the spleen, macrophages)
Other processes  
Serious infections T cells (delayed decrease in hypersensitivity), phagocytic system (defect of neutrophil destruction after severe bacterial infections)
Burns B and T cells
Malnutrition T cells
Malignant processes T cells
Mellitus diabetes Phagocytic system (decreased neutrophil chemitaxis)
Systemic lupus erythematosus T cells, complement
Nephrotic syndrome Decreased immunoglobulins due to hypercatabolism
Neutropenia, pancytopenia Decreased phagocytosis
PAGE T cells

Acquired Immune Deficiency Syndrome (AIDS)

In June 1981 to the Center for Disease Control in Atlanta, USA, cases of opportunistic infectious hypoallergent pneumonia carinii , and patients with disseminated Kaposi's sarcomas whose common denominator was that of being young men with no history of disease and with homosexual behavior . Later the picture was seen in intravenous drug addicts who injected themselves in groups.

All had a deficit in cellular immunity. Over time, Haitians, hemophiliacs and transfused people, female partners of people with AIDS, children of couples with AIDS, prostitutes, etc. were added.

It was not until May 1983 that Luc Montagnier (France) isolated the virus while Robert Gallo reported his work referring to the fact that he had isolated it in November 1982. Isolation of the virus allowed the detection of antibodies against said microorganism, which were found in almost 100% of AIDS patients. Today the disease takes the form of a pandemic that involves all countries and all races.

It was not until 1986 that the international nomenclature designated it as HIV, the human immunodeficiency virus. It is a thermosensitive retrovirus (it is inactivated when exposed to 56ºC for 30 minutes and can also be inactivated with ether or 0.5% sodium hypochlorite

Pathophysiology

A significant decrease in the CD4 + lymphocyte population was demonstrated in all patients and it was considered that these were destroyed by the virus. This CD4 + lymphocyte molecule constitutes one of the specific receptors for HIV, but the virus is only found in a small virus CD4 + T lymphocytes, which shows that there is some difficulty for the microorganism to penetrate the cell.

In addition, the virus can be found in other cells such as B lymphocytes, dendritic ganglion cells, and monocytic cells and the central nervous system. For all this, it is considered that in the pathophysiology there is an autoimmune mechanism that would justify the different clinical forms of HIV positive, since not all develop disease. When the patient develops classic AIDS, he shows an alteration of all the cells that normally participate in an immune response.

Clinic: Questioning

In the interrogation, those data transmitted by the patient that suggest the pathology produced by HIV should be asked and developed. You must find out about risk behaviors to acquire the disease. The use of prophylactic, sexual diseases suffered in recent times. Ask about the number of sexual partners in the last year (heterosexual and homosexual, genital, rectal and oral connections). Occasional, anonymous sexual partners and prostitutes. The use of injectables, drugs, and if their administration was shared. It is important to detect information on transfusions prior to the 1990s.

Related symptoms to consider are: prolonged fever without a definite cause, anorexia, weight loss, decay and fatigue without a clear cause. Myalgia.

Consider the presence of unusual, recurrent, or refractory infections (TBC, Pneumocystis, herpes, pneumococci, cryptococci, toxoplasmosis, cytomegalovirus). Eye conditions, scotomas. Oropharyngeal ulcers, oral and / or vaginal mucosal mycosis, odynophagia, loss of taste.

Skin rash, scabs, eczema, papules, can be the guiding data. Productive or dry cough, chronic dyspnea, chronic diarrhea, blood in stool, nonspecific abdominal pain. Headaches with increased pressure (Valsalva). Seizures and neurological deficits, tingling, and loss of muscle mass.

Physical exam

The signs to find through the physical examination, which guide us to think about this pathology, are when controlling the vital signs (temperature, pulse rate and respiration, as well as weight). Thorough examination of the mouth, tongue and oropharynx to detect lesions, ulcers, secretions, canker sores, vesicles, leukoplakia, etc. The skin should be observed for eruptions, psoriasis, dryness, seborrhea, dandruff, acne, blemishes, hemorrhagic suffusions. The areas of the neck, armpits and groin should be palpated in search of adenopathies that are characterized by being painless, superficial and multiple. Examination of the chest should be oriented to detect signs of respiratory infection. The abdomen should be palpated for liver or splenomegaly. In the pelvic rectal area, detect peri-anal or vaginal secretions, ulcers, vesicles (herpes), peri-rectal abscesses. Examine the psychic state as neurological, motor and sensitive.

HIV is capable of generating a variety of clinical pictures. They are classified into groups and categories according to the US Center for Disease Control.

Group I. acute infection. it is a picture similar to that of mononucleosis with fever, enanthema, adenopathy, and sometimes meningism and splenomegaly. In a syndrome associated with seroconversion

Group II. Asymptomatic infection. It is characterized by the absence of symptoms and positive serology. Individuals in this group are at high risk because they infect, but since they have no symptoms, they ignore their infectious status.

Group III. Existing generalized lymphadenopathy. Adenomegaly of more than 1cm in 2 or more extrainguinal sites of more than 12 weeks of evolution.

Group IV. AIDS. In all of them, HIV is positive. It includes a wide variety of patients, from those with minimal manifestations to the seriously ill.

Subgroup A. fever of more than one month of evolution and / or weight loss greater than 10%, and / or diarrhea of ​​more than one month.

Subgroup B. dementia, and / or myelopathy, and / or peripheral neuropathy.

Subgroup C. Secondary infectious diseases, including the major markers or category C1 that are: pneumonia pneumosystis carinii, extraintestinal strongyloidiasis, cryptosporidiosis, isosporiasis, candidiasis (esophageal, bronchial or pulmonary), cryptococcosis, histoplasmosis, infections due to atypical mycobacteria, herpes simplex, hertoplasmosis chronic or disseminated mucocuraneo), progressive multifocal leukoencephalopathy. The other minor markers, or category C2, are: oral leukoplakia, multidermatomic herpes zoster, recurrent salmonellosis, nocardiosis, tuberculosis, oral candidiasuis

Subgroup D. includes one or more of the following tumors: Kaposi's sarcoma, Hodgkin's lymphoma, primary lymphoma of the brain.

Subgroup E. Other diseases not classified in the preceding groups, attributable to HIV and indicative of a deficit in cellular immunity.

In June 1987, at the III International AIDS Conference, the classification was broadened to include: 1) the demential complex of AIDS, 2) the extreme cachexia syndrome due to ICH, and 3) disseminated tuberculosis in HIV-positive individuals (the latter It is very important in our country, since tuberculosis has a high incidence compared to that of developed countries).

The world HIV positive population is estimated at 10,000,000 people; in the US there are 1,000,000 and in the rest of America 900,000 carriers of the virus.

In conclusion, to diagnose AIDS it is necessary to verify a positive seriology and a combination of the following elements: belonging to a risk group, decrease in inducing T lymphocytes and / or decrease in the T4 / T8 ratio; and presence of opportunistic infections and / or specific marker tumors.

Study methodology

HIV-1 / HIV-2 ELISA: Sensitivity:> 99.5 Specificity:> 99.8: First study to screen for HIV infection Must be confirmed.
HIV-1 Western blot: Sensitivity:> 96 Specificity> 99.9: Most accurate method to confirm antibodies. Predictive value> 99% in high and low risk populations
Plasma HIV RNA: Not approved as a diagnostic test, but useful for follow-up
Plasma P24 antigen: Not approved as a diagnostic test. It is useful in Acute Retroviralis Syndrome
CD4 absolute count: CD4 + cell depletion is characteristic but not diagnostic. It is useful for prognosis and response to treatment.
Basal Genotype: Obtain it before starting retroviral treatment
CBC with differential and platelets: It is required to calculate the absolute CD 4 count. Leukopenia, anemia, and thrombocytopenia are frequent complications of the disease.
General chemistry with enzymes: Hepatobiliary and pancreatic complications are frequent
Lipid panel (cholesterol, triglycerides, HDL): Patients in treatment increase lipid levels due to drugs that are inhibitors of proteases
VDRL or other diagnostic tests for Syphilis
Hepatitis Serology
CMV IgG: No routine. Most have a high prevalence (90%) of positive
PPD serology : It may not be reliable in advanced stage
Toxoplasma IgG by serology
Chest X-ray: Considered a baseline study