An overwhelming post-splenectomy infection (OPSI) or Overwhelming post-splenectomy sepsis (OPSS) is a rare but rapidly fatal infection occurring in individuals following removal of the spleen. The infections are typically characterized by either meningitis or sepsis, and are caused by encapsulated organisms including "Streptococcus pneumoniae".

The risk of OPSI is 0.23–0.42 percent per year, with a lifetime risk of 5 percent. Most infections occur in the first few years following splenectomy, but the risk of OPSI is lifelong. OPSI is almost always fatal without treatment, and modern treatment has decreased the mortality to approximately 40–70 percent. Individuals with OPSI are most commonly treated with antibiotics and supportive care. Measures to prevent OPSI include vaccination and prophylactic antibiotics.

Immune reconstitution inflammatory syndrome (IRIS) (also known as immune recovery syndrome) is a condition seen in some cases of AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

The spleen contains many macrophages (part of the reticuloendothelial system), which are immune cells that phagocytose (eat) and destroy bacteria. In particular, these macrophages are activated when bacteria are bound by IgG antibodies (IgG1 or IgG3) or the complement component C3b. These types of antibodies and complement are immune substances called opsonizers, molecules that bind to the surface of bacteria to facilitate phagocytosis.

When the spleen is no longer present (asplenia), IgG and C3b are still bound to bacteria, but they cannot be removed from the blood circulation due to the loss of the splenic macrophages. Hence the bacteria are free to cause infection.

Patients without spleens often need immunizations against pathogens that normally require opsonization and phagocytosis by macrophages in the spleen. These include common human pathogens with bacterial capsules ("Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella pneumoniae"). Capsules made of polysaccharides (sugars) permit bacteria to evade phagocytosis by macrophages alone, since only proteins are directly recognized by macrophages in phagocytosis. So humoral immunity in forms of IgG and complement proteins is the human immune system's response against bacterial capsules.

Waterhouse-Friderichsen Syndrome can be caused by a number of different organisms (see below). When caused by Neisseria meningitidis, WFS is considered the most severe form of meningococcal sepsis. The onset of the illness is nonspecific with fever, rigors, vomiting, and headache. Soon a rash appears; first macular, not much different from the rose spots of typhoid, and rapidly becoming petechial and purpuric with a dusky gray color. Low blood pressure (hypotension) develops and rapidly leads to septic shock. The cyanosis of extremities can be extreme and the patient is very prostrated or comatose. In this form of meningococcal disease, meningitis generally does not occur. Low levels of blood glucose and sodium, high levels of potassium in the blood, and the ACTH stimulation test demonstrate the acute adrenal failure. Leukocytosis need not be extreme and in fact leukopenia may be seen and it is a very poor prognostic sign. C-reactive protein levels can be elevated or almost normal. Thrombocytopenia is sometimes extreme, with alteration in prothrombin time (PT) and partial thromboplastin time (PTT) suggestive of disseminated intravascular coagulation (DIC). Acidosis and acute kidney failure can be seen as in any severe sepsis. Meningococci can be readily cultured from blood or cerebrospinal fluid, and can sometimes be seen in smears of cutaneous lesions. Difficulty swallowing, atrophy of the tongue, and cracks at the corners of the mouth are also characteristic features.

Pneumococcal infection is an infection caused by the bacterium "Streptococcus pneumoniae". "S. pneumoniae" is a common member of the bacterial flora colonizing the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. However, it is also the cause of significant disease being a leading cause of pneumonia, bacterial meningitis, and sepsis. The World Health Organization estimate that in 2005 pneumococcal infections were responsible for the death of 1.6 million children worldwide.

Asplenia is a form of immunodeficiency, increasing the risk of sepsis from polysaccharide encapsulated bacteria, and can result in overwhelming post splenectomy infection (OPSI), often fatal within a few hours. In particular, patients are at risk from "Streptococcus pneumoniae", "Haemophilus influenzae", and meningococcus. The risk is elevated as much as 350–fold.

The risk to asplenic patients has been expressed as equivalent to an adult dying in a road traffic accident (in every 100 people without spleens, 1 to 5 would develop a severe infection per decade) (reference UK Splenectomy Trust Advice)—hence sensible precautions are advisable. Increased platelet counts can be seen in individuals without a functioning spleen.

Asplenia refers to the absence of normal spleen function and is associated with some serious infection risks. Hyposplenism is used to describe reduced ('hypo-') splenic functioning, but not as severely affected as with asplenism.

Waterhouse–Friderichsen syndrome (WFS) is defined as adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection: Typically it is caused by "Neisseria meningitidis".

The bacterial infection leads to massive bleeding into one or (usually) both adrenal glands. It is characterized by overwhelming bacterial infection meningococcemia leading to massive blood invasion, organ failure, coma, low blood pressure and shock, disseminated intravascular coagulation (DIC) with widespread purpura, rapidly developing adrenocortical insufficiency and death.

IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.

IRIS has been described in immunocompetent hosts who have meningitis caused by "Cryptococcus gattii" and "Cryptococcus neoformans" var. "grubii", environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.

Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.

The increasing inflammation can cause brain injury or be fatal.

The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases:

1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance;

2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and

3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.

Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:

1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count);

2. elevated C-reactive protein;

3. failure to sterilize the CSF before immune recovery.

IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom "Cryptococcus neoformans" is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.

Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophil granulocytes in the blood.

Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of neutrophilia is a bacterial infection, especially pyogenic infections.

Neutrophils are also increased in any acute inflammation, so will be raised after a heart attack, other infarct or burns.

Some drugs, such as prednisone, have the same effect as cortisol and adrenaline (epinephrine), causing marginated neutrophils to enter the blood stream. Nervousness will very slightly raise the neutrophil count because of this effect.

A neutrophilia might also be the result of a malignancy. Chronic myelogenous leukemia (CML or chronic myeloid leukaemia) is a disease where the blood cells proliferate out of control. These cells may be neutrophils. Neutrophilia can also be caused by appendicitis and splenectomy.

Primary neutrophilia can additionally be a result of Leukocyte adhesion deficiency.

"S. pneumoniae" is responsible for 15–50% of all episodes of community acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bloodstream infections and bacterial meningitis.

As estimated by WHO in 2005 it killed about 1.6 million children every year worldwide with 0.7–1 million of them being under the age of five. The majority of these deaths were in developing countries.

The clinical hallmark is haemorrhagic bullae on the mucosa of the oronasopharynx. Haemorrhage from ruptured bullae, epistaxis or gastrointestinal bleeding is severe and may cause shock and death.

Onyalai is an acute disease that results in the development of hemorrhagic lesions on oral, nasal, and subconjunctival mucous membranes and skin, including on the soles of the feet. The patient initially is not in distress, which may result in a delay of diagnosis. As the disease progresses, hematuria, melena and menorrhagia may develop. Bleeding usually persists for approximately eight days, and may recur. Approximately 80 percent of cases will develop chronic thrombocytopenia. Periodic episodes of acute hemorrhage are possible and may be severe, leading to shock and death.

Subphrenic abscess is a disease characterized by an accumulation of infected fluid between the diaphragm, liver, and spleen. This abscess develops after surgical operations like splenectomy.

Presents with cough, increased respiratory rate with shallow respiration, diminished or absent breath sounds, hiccups, dullness in percussion, tenderness over the 8th–11th ribs, fever, chills, anorexia and shoulder tip pain on the affected side. Lack of treatment or misdiagnosis could quickly lead to sepsis, septic shock, and death. It is also associated with peritonitis.

Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. In the acute phase (also known as Oroya fever or "fiebre de la Oroya"), "B. bacilliformis" infection is a sudden, potentially life-threatening infection associated with high fever and decreased levels of circulating red blood cells (i.e., hemolytic anemia)and transient immunosuppression. "B. bacilliformis" is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many bacilli adherent to red blood cells. Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinal meningitis, or paralysis. It is seen in 20% of patients with acute infection, in which the prognosis is very guarded with an about 50% mortality. The most feared complication is overwhelming infection mainly by Enterobacteriaceae, particularly "Salmonella" (both "S. typhi" and " S. "non-"typhi", as well as reactivation of toxoplasmosis and other opportunistic infections .

The chronic manifestation consists of a benign skin eruption with raised, reddish-purple nodules (angiomatous tumours). The bacterium can be seen microscopically, if a skin biopsy is silver stained (the Warthin–Starry method).

Pneumococcal septicemia, or whole-body infection caused by the "Streptococcus pneumoniae" bacteria, has been reported to cause autosplenectomy but is a very rare and poorly understood complication of the infection.

"B. henselae" is the etiologic agent for peliosis hepatis, which is defined as a vascular proliferation of sinusoid hepatic capillaries resulting in blood-filled spaces in the liver in HIV patients and organ transplant recipients. Peliosis hepatis can be associated with peliosis of the spleen, as well as bacillary angiomatosis of the skin in HIV patients.

The most frequent cause of autosplenectomy is sickle cell anemia which causes progressive splenic hypofunction over time. Increased deoxygenation causes sickling of red blood cells, which adhere to the spleen wall and splenic macrophages causing ischemia. This ischemia can result in splenic sequestration, where large amounts of blood pool in the spleen but do not flow within vasculature. This lack of blood flow can cause atrophy in the spleen and can lead to autosplenectomy.

Onyalai is an acquired form of immune thrombocytopenia which differs clinically, epidemiologically and immunologically from idiopathic thrombocytopenic purpura.

Lymphocytosis is an increase in the number of lymphocytes in the blood. In adults, lymphocytosis is present when the lymphocyte count is greater than 4000 per microliter (4.0 x 10(9)/L), in older children greater than 7000 per microliter and in infants greater than 9000 per microliter. Lymphocytes normally represent 20 to 40% of circulating white blood cells.

Lymphocytosis is usually detected when a complete blood count is obtained. If not provided the lymphocyte count can be calculated by multiplying the total white blood cell (WBC) count by the percentage of lymphocytes found in the differential count. The lymphocyte count can also be directly measured by flow cytometry.

Neonatal conjunctivitis by definition presents during the first month of life. It may be infectious or non infectious. In infectious conjunctivitis, the organism is transmitted from the genital tract of an infected mother during birth or by infected hands.

- Pain and tenderness in the eyeball.

- Conjunctival discharge: purulent, mucoid or mucopurulent depending on the cause.

- Conjunctiva shows hyperaemia and chemosis. Eyelids are usually swollen.

- Corneal involvement (rare) may occur in herpes simplex ophthalmia neonatorum.

The most common symptoms include headache, muscle aches, and fatigue. A rash may occur, but is uncommon. Ehrlichiosis can also blunt the immune system by suppressing production of TNF-alpha, which may lead to opportunistic infections such as candidiasis.

Most of the signs and symptoms of ehrlichiosis can likely be ascribed to the immune dysregulation that it causes. A "toxic shock-like" syndrome is seen in some severe cases of ehrlichiosis. Some cases can present with purpura and in one such case the organisms were present in such overwhelming numbers that in 1991 Dr. Aileen Marty of the AFIP was able to demonstrate the bacteria in human tissues using standard stains, and later proved that the organisms were indeed Ehrlichia using immunoperoxidase stains.

Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.

3% of human monocytic ehrlichiosis cases result in death; however, these deaths occur "most commonly in immunosuppressed individuals who develop respiratory distress syndrome, hepatitis, or opportunistic nosocomial infections."

Lymphocytosis is a feature of infection, particularly in children. In the elderly, lymphoproliferative disorders, including chronic lymphocytic leukaemia and lymphomas, often present with lymphadenopathy and a lymphocytosis.

Causes of absolute lymphocytosis include:

- acute viral infections, such as infectious mononucleosis (glandular fever), hepatitis and Cytomegalovirus infection

- other acute infections such as pertussis

- some protozoal infections, such as toxoplasmosis and American trypanosomiasis (Chagas disease)

- chronic intracellular bacterial infections such as tuberculosis or brucellosis

- chronic lymphocytic leukemia

- acute lymphoblastic leukemia

- lymphoma

- post-splenectomy state

- smoking

Causes of relative lymphocytosis include: age less than 2 years; acute viral infections; connective tissue diseases, thyrotoxicosis, Addison's disease, and splenomegaly with splenic sequestration of granulocytes.

Fever and a non specific skin eruption – with reddening (erythema) and swelling (oedema) of the skin – are the most common symptoms of NEH. Patients usually present with the skin eruption 1-2 weeks after use of the cytotoxic drug. Sometimes, the skin eruption can be painful. Skin eruptions can be located on the extremities, trunk, and face. Severe lesions are rare, and can mimic cellulitis. Generalised lesions resembling erythema multiforme have been reported.

A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months.

Cold agglutinin mediated acrocyanosis differs from Raynaud phenomenon. In Raynaud phenomena, caused by vasospasm, a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease.

Other symptoms

- Respiratory symptoms: May be present in patients with "M pneumoniae" infection.

- Hemoglobinuria (the passage of dark urine that contains hemoglobin), A rare symptom that results from hemolysis, this may be reported following prolonged exposure to cold, hemoglobinuria is more commonly seen in paroxysmal cold hemoglobinuria.

- Chronic fatigue, Due to anemia.