Discuss Immunosuppressed states&opportunistic infections
Define what is meant by an immunocompromised host and opportunistic infections
Immunocompromised host=immunodeficiency host=immunosuppressed host
Definition: A state in which a person's immune system is weakened or absent.
An immunocompromised host is a patient who does not have the ability to respond normally to an infection due to an impaired or weakened immune system. This inability to fight infection can be caused by a number of conditions including illness and disease (e.g. diabetes, HIV), malnutrition, and drugs.
Individuals who are immunocompromised are less capable of battling infections because of an immune response that is not properly functioning. Examples of immunocompromised people are those that have HIV or AIDS, are pregnant, or are undergoing chemotherapy or radiation therapy for cancer. Other conditions, such as certain cancers and genetic disorders, can also cause a person to become immunocompromised. Immunocompromised individuals can sometimes be prone to more serious infections and/or complications than healthy people. They are also more prone to getting opportunistic infections, which are infections that do not normally afflict healthy individuals.
What Is an Immunodeficiency Disorder?
Immunodeficiency disorders prevent your body from being able to fight infections and diseases the way it should. An immunodeficiency disorder makes you considerably more susceptible to catching microbial agents.
Immune disorders are oftentimes categorized as either congenital or acquired. Whenany one born with a disorder, it’s sometimes called a congenital or primary disorder. Acquired disorders are sometimes called secondary disorders. Secondary disorders are more common than primary.
Causes for Immunodeficiency:
It is important to note that not all immunodeficiency states result in the same risk for infection.
Who Is at Risk For Immunodeficiency Disorders?
-People who have a family history of primary disorders are at a higher than normal risk for them.
-Anything that weakens your immune system can lead to a secondary immunodeficiency disorder. For example, the exposure to body fluids such as blood and sperm from someone infected with HIV can cause AIDS.
-Removing the spleen can weaken your immune system. Spleen removal may be required in response to one of any number of diseases or injuries, including cirrhosis of the liver, sickle cell anemia, or trauma to the spleen. Aging also weakens your immune system. As you age, some of the organs that produce white blood cells shrink and produce fewer of them.
-Proteins are important to your immunity. An insufficient amount of protein in the diet can reduce the strength of your immune system. Additionally, when you sleep, your body produces proteins that help your immune system fight infection. For this reason, lack of sleep reduces your immune defenses.
-Cancers and the chemotherapy drugs used to treat them can reduce your immunity.
The following diseases and conditions are also linked to immunodeficiency disorders:
1-Ataxia-telangiectasia
2-Chediak-Higashi syndrome
3-Combined immunodeficiency disease
4-Complement deficiencies
5-DiGeorge syndrome
6-Hypogammaglobulinemia
7-Job syndrome
8-leukocyte adhesion defects.
9-panhypogammaglobulinemia
10-Bruton’s disease
11-Congenital agammaglobulinemia
12-Selective deficiency of IgA
13-Wiskott-Aldrich syndrome.
What Are the Different Types of Immunodeficiency Disorders?
Primary immunodeficiency disorders are immune disorders you are born with.
Primary disorders include:
-X-linked agammaglobulinemia (XLA)
-Severe combined immunodeficiency (SCID disorders)
-Common variable immunodeficiency.
-Alymphocytosis (“boy in a bubble” disease)
Secondary disorders
Can be happen when your body is attacked by an outside source, such as :
-Toxic chemical.
-Severe infection, such as viral hepatitis
-Severe burns and radiationalso can cause secondary disorders.
-Chronicdebilitating diseases as diabetes, Ischemic heart diseases & chronic renal diseases as chronic pyelonephritis.
-AIDS.
-Cancers of the immune system, such as leukemia.
-Immune complex diseases,
-Multiple myeloma.
Clinical features suggestive of a primary immunodeficiency:
The following features should lead to suspicion of an immunodeficiency and consideration of referral to an immunology specialist for evaluation:
*Family history of immunodeficiency or unexplained early death (e.g., before age 30)
*Failure to gain weight or grow normally (failure to thrive).
*Need for intravenous antibiotics and/or hospitalization to clear infections.
*Six or more new infections within one year.
*Two or more serious sinus infections or pneumonias within one year.
*Four or more new ear infections within one year.
*Two or more episodes of sepsis or meningitis in a life time.
*Two or more months of antibiotics with little effect.
*Recurrent or resistant candidiasis.
*Recurrent tissue or organ abscesses.
*Infection with an opportunistic organism.
*Complications from a live vaccine (e.g., rotavirus, varicella, and Bacillus Calmette-Guerin vaccines)
*Chronic diarrhea.
*Nonhealing wounds.
*Extensive skin lesions.
*Persistent lymphopenia (a count of <1500 cells/uL in patients over five years and <2500 cells/uL in younger children).
*Unexplained autoimmunity or fevers.
*Granulomas.
*Hemophagocytic lymphohistiocytosis (HLH).
*Lymphoma in infancy.
*Features typical of syndromic primary immunodeficiencies (e.g., cartilage-hair hypoplasia, Chediak-Higashi syndrome, and ataxia-telangiectasia) (see "Syndromic immunodeficiencies")
*Family history of immunodeficiency was the most predictive factor of any primary immunodeficiency (PID) in a retrospective survey of 563 children who presented to two pediatric immunodeficiency centers for evaluation of possible PID. In addition, the use of intravenous antibiotics for sepsis and failure to thrive were strong identifiers of neutrophil PID and T cell PID, respectively.
In infants, additional features suggestive of a primary immunodeficiency include hypocalcemia with or without seizures, congenital heart defects (mainly coronotruncal anomalies), absence of thymic shadow on chest radiograph , and delayed umbilical cord detachment (>30 days) .
Severe combined immunodeficiency (SCID) is considered a pediatric emergency, and special precautions should be taken if this diagnosis is suspected.
Pathogens responsible for infections in immunocompromised hosts:
In addition to organisms that may typically infect normal hosts, immunocompromised patients have increased susceptibility to infections with organisms of little native virulence in normal individuals. The differential diagnosis of potential infections in the immunocompromised host is broad and may include:
Encapsulated bacteria (i.e. Streptococcus pneumonia, Neisseria meningitides, Haemophilus influenza type B, Group B Streptococcus, Klebsiella pneumonia, Salmonella typhi) are of great concern with underlying induced humoral immunodeficiency with accompanying diminished opsonizing capacity
Nocardia, Staphylococcus and Burkoholderia infections are more common in patients with neutrophil dysfunctions and neutropenia
Intracellular bacteria – Mycobacteria (M. tuberculosis, M. avium intracellulare), Legionella, Nocardia
Yeast – Histoplasma, Cryptococcus, Coccidiomycocis, Pneumocystic jirovecii
Mold – Aspergillus, Scedosporium, Mucormycosis
Viral – Cytomegalovirus (CMV), Influenza, respiratory syncytial virus, human metapnuemovirus, varicella and herpes simplex
Parasitic – Toxoplasma, Strongyloides
HUMORAL IMMUNE DYSFUNCTION:
Patients with humoral immune dysfunction, particularly primary immunoglobulin and complement deficiencies, are at risk for chronic sinus, pulmonary, and gastrointestinal infections. Frequent pathogens include Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, Salmonella species, Mycoplasma species, Giardia, rotavirus, and enteroviruses. Conditions often included in this group of disorders are functional or anatomic asplenia, and hypogammaglobulinemic states which can be congenital or due to conditions such as multiple myeloma, Waldenstrom's macroglobulinemia, lymphoma, and chronic lymphocytic leukemia.
Splenic dysfunction — Patients without a spleen or with hypofunction of the spleen are at increased risk for infection due to defects in antibody production, decreased ability to remove bacteria from the blood, and decreased production of important opsonin-associated proteins like tuftsin . Conditions associated with functional hyposplenia include systemic lupus erythematosus (SLE), rheumatoid arthritis, graft versus host disease, amyloidosis, celiac disease, ulcerative colitis, sickle cell anemia, hereditary spherocytosis (SC), and hemoglobin SC disease.
These patients are particularly susceptible to infection with encapsulated bacteria such as S. pneumoniae,N. meningitidis, and H. influenzae. Skin and soft tissue infections due to S. pneumoniae may include cellulitis, pyomyositis, rhabdomyolysis, subcutaneous abscess, peripheral gangrene, and livedo reticularis/acrocyanosis. Skin manifestations of meningococcal infection typically include blanching erythematous macules that later become petechial or purpuric. In the patient with disseminated intravascular coagulation and overwhelming postsplenectomy infections due to S. pneumoniae and N. meningitidis, petechial/purpuric lesions may progress to hemorrhagic bullae and peripheral gangrene (ie, purpura fulminans). H. influenzae, Capnocytophaga spp, Enterobacteriaceae, and group A and B streptococci should also be included as possible pathogens in this setting.
CELL-MEDIATED IMMUNE DYSFUNCTION
— Patients with cell-mediated immune (CMI) dysfunction are at increased risk of infection with a myriad of intracellular bacteria and mycobacteria, viruses, fungi, and parasites. Though primarily important in the control of intracellular pathogens, suppression of CMI can also predispose to infections with extracellular pathogens such as Pneumocystis jirovecii (formerly P. carinii), Strongyloides, and Candida spp.
Affected components / Main causes / Main pathogens of resultant infectionsHumoral immune deficiency / B cells, plasma cells or antibodies / Primary humoral
Multiple myeloma
Chronic lymphoid leukemia
AIDS / Streptococcus pneumoniae
Hemophilus influenzae
Pneumocystis jirovecii
Giardia intestinalis
Cryptosporidium parvum
T cell deficiency / T cell / Marrow and other transplantation
AIDS
Cancer chemotherapy
Lymphoma
Glucocorticoid therapy / Intracellular pathogens, including Herpes simplex virus, Mycobacterium, Listeria, and intracellular fungal infections.
Neutropenia / Neutrophil granulocytes / Chemotherapy
Bone marrow transplantation
Dysfunction, such as chronic granulomatous disease / Enterobacteriaceae
Oral Streptococci
Pseudomonas aeruginosa
Enterococcus species
Candida species
Aspergillus species
Asplenia / Spleen / Splenectomy
Trauma
Sickle-cell anemia / Polysaccharide encapsulated bacteria, particularly:
Streptococcus pneumoniae
Haemophilus influenza,
Neisseria meningitidis
Plasmodium species
Babesia species
Complement deficiency / Complement system / Congenital deficiencies / Neisseria species
Streptococcus pneumonia
What Is the Outlook for Someone With an Immunodeficiency Disorder?
Most doctors agree that people with immunodeficiency disorders can lead full and productive lives. Early identification and treatment of the disorder and the problems it causes are very important.
How Can Immunodeficiency Disorders Be Prevented?
Primary disorders can be controlled and treated, but not prevented.
Secondary disorders can be prevented in a number of ways. For example, it is possible to avoid AIDS by not having unprotected sex with someone who carries the virus.
Sleep is very important to a healthy immune system. According to the Mayo Clinic, adults need about eight hours of sleep per night (Mayo Clinic, 2012).
If your immune system is not working properly, it is important that you stay away from people who are sick.
If you have a contagious immune disorder like AIDS, you can keep others healthy by practicing safe sex and not sharing bodily fluids with people who don’t have the condition.
If your doctor thinks you might have an immunodeficiency disorder, he or she will want to do a thorough medical exam including:
-medical history
-physical exam
-T cell count
-white blood cell count
-Vaccines can be used to test your immune system response in what is called an antibody test. Your doctor will give you a vaccine and make an appointment in a few days or weeks to test your blood for its response to the vaccine. If you don’t have an immunodeficiency disorder, your immune system will produce antibodies to fight the organisms in the vaccine. You might have a disorder if your blood test doesn’t show antibodies.
How Are Immunodeficiency Disorders Treated?
Each disorder will be treated according to the specific conditions it causes. For example, AIDS causes several different infections, including Kaposi’s sarcoma, which is treated with doxorubicin lipid complex, and cryptococcosis, which is treated with fluconazole.
Treatment for immunodeficiency disorders commonly includes antibiotics and antibody replacement. A drug called interferon is often used to treat the viral infections caused by a disorder.
If your bone marrow is not producing enough lymphocytes, your doctor might order a bone marrow transplant.
What Is the Outlook for Someone With an Immunodeficiency Disorder?
Most doctors agree that people with immunodeficiency disorders can lead full and productive lives. Early identification and treatment of the disorder and the problems it causes are very important.
Examples of persons with weakened immune systemsinclude those with AIDS; cancer and transplant patients who are taking certain immunosuppressive drugs; and those with inherited diseases that affect the immune system (e.g., congenital agammaglobulinemia, congenital IgA deficiency). The risk of developing severe disease may differ depending on each person's degree of immune suppression. Following all the recommendations in this fact sheet can be a great personal burden, so consult with your health care provider to determine whether your medical condition makes it advisable to follow all of these recommendations.
Immunosuppressed Persons
CD4+ cell count <200/uL / More likely to develop diarrhea and other symptoms that last for a long timeCD4+ cell count >200/uL / -Symptoms may last 1 to 3 weeks, or slightly longer
-May carry Crypto parasites in their intestines, but have no symptoms (these people could infect other people)
-If their CD4+ counts drop below 200/uL, their symptoms might reappear.
Sepsis, severe sepsis and septic shock are major healthcare problems. Immunocompromised hosts are particularly more prone to infections. Though the initial management of severe sepsis and septic shock may not be greatly affected by the immune status, the spectrums of opportunistic offending infectious causes are greater. The etiologies, clinical manifestations, diagnostic criteria, microbiology and treatment options for severe sepsis in immunocompromised hosts must be revised well for each case.
Sepsis is defined as a suspected or documented infection in the presence of signs of systemic inflammation such as:
-Hyperthermia (>38.3°C) or hypothermia (<36°C).
-Tachycardia
-Tachypnea.
-Altered mentation.
-Leucocytosis or leucopenia.
-Normal WBC count with greater than 10% immature forms (i.e. bands)
-Plasma C-reactive protein more than two SD above the normal value.
-Plasma procalcitonin more than two SD above the normal.
Esophagitis
Esophageal candidiasis is an opportunistic infection of the esophagus by Candida albicans. The disease usually occurs in patients in immunocompromised states, including post-chemotherapy and in AIDS. However, it can also occur in patients with no predisposing risk factors, and is more likely to be asymptomatic in those patients.[1] It is also known as candidal esophagitis or monilial esophagitis.
Clinical presentation
Patients with esophageal candidiasis present with odynophagia, or painful swallowing. Longstanding esophageal candidiasis can result in weight loss. There is often concomittant thrush.
Some patients present with esophageal candidiasis as a first presentation of systemic candidiasis.
Diagnosis
In most cases the diagnosis is established based on response to therapy. Patients in whom esophageal candidiasis is suspected should receive a brief course of antifungal therapy with fluconazole. If the infection resolves after treatment with fluconazole, then the diagnosis of esophageal candidiasis is made and no further investigation is needed. However, if the infection persists or if there are other factors involved which may warrant further investigation, then patient will undergo an esophagogastroduodenoscopy if it is safe to do so. Endoscopy often reveals classic diffuse raised plaques that characteristically can be removed from the mucosa by the endsocope. Brushing or biopsy of the plaques shows yeast and pseudohyphae by histology that are characteristic of Candida species.
Therapy
The current first-line treatment is fluconazole, 200 mg. on the first day, followed by daily dosing of 100 mg. for at least 21 days total. Treatment should continue for 14 days after relief of symptoms. [Note: this page previously listed first-line treatment using a single dose of fluconazole (750 mg), but that is actually treatment for oropharyngeal, not esophageal Candidiasis.[2]] Other therapy options include:
nystatin
other oral triazoles, such as itraconazole
caspofungin, used in refractory or systemic cases
amphotericin, used in refractory or systemic cases
References
-Mimidis, K; Papadopoulos, V; Margaritis, V; Thomopoulos, K; Gatopoulou, A; Nikolopoulou, V; Kartalis, G (February 2005). "Predisposing factors and clinical symptoms in HIV-negative patients with Candida oesophagitis: are they always present?". International journal of clinical practice 59 (2): 210–3. doi:10.1111/j.1742-1241.2004.00249.x. PMID 15854199.
-Hamza OJM, Matee MIN, Brüggemann RJM, et al. (2008). "Single-dose fluconazole versus standard 2-week therapy for oropharyngeal candidiasis in HIV-infected patients: A randomized, double-blind, double-dummy trial". Clin Infect Dis 47 (10): 1270–1276. doi:10.1086/592578. PMID 18840077.
Common forms of esophagitis include reflux esophagitis, infectious esophagitis, pill esophagitis, eosinophilic esophagitis, and radiation and chemoradiation esophagitis. Candida esophagitis is the most common type of infectious esophagitis. The prognosis is good with rapid diagnosis and proper treatment; ultimately, it depends on the underlying disease. Esophagitis is commonly seen in adults and is uncommon in childhood.
Essential update: Children who have outgrown IgE-mediated allergy to a food may be predisposed to develop eosinophilic esophagitis in reaction to that food
In a study of 1025 children with eosinophilic esophagitis, Maggadottir and colleagues found that individuals who have outgrown IgE-mediated food allergies may develop eosinophilic esophagitis as a reaction to the same foods. The researchers identified specific foods, most commonly milk, egg, wheat, and soy, as causing eosinophilic esophagitis in 425 children, of whom 17 developed an eosinophilic esophagitis reaction to a particular food after they outgrew an allergy to that same food.[1, 2]
Signs and symptoms
The history findings vary according to the type of esophagitis present. Symptoms of reflux esophagitis (the most common type) may include the following:
- Heartburn, or dyspepsia (the most common symptom)
-Water brash[3]
-Regurgitation
-Other common symptoms, including upper abdominal discomfort, nausea, bloating, and fullness
-Less common symptoms, including dysphagia, odynophagia, cough, hoarseness, wheezing, and hematemesis
-Chest pain indistinguishable from that of coronary artery disease (CAD)