As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include:

- Severe hemorrhage (retroperitoneal hemorrhage)

- Drugs

- Use of sulfa drugs

- Use of dapsone

- Use of glucocorticoids

- Use of G-CSF or related growth factors

- All-trans retinoic acid (ATRA)

- Ethylene glycol intoxication

- Infections

- Clostridium difficile

- Tuberculosis

- Pertussis

- Infectious mononucleosis (lymphocyte predominant)

- Visceral larva migrans (eosinophil predominant)

- Asplenia

- Diabetic ketoacidosis

- Organ necrosis

- Hepatic necrosis

- Ischemic colitis

- As a feature of trisomy 21 in infancy (incidence of ~10%)

- As a paraneoplastic phenomenon (rare)

The term leukemoid reaction describes an increased

white blood cell count, or leukocytosis, which is a physiological response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood.

It may be lymphoid or myeloid.

The way CML presents depends on the stage of the disease at diagnosis as it has been known to skip stages in some cases.

Most patients (~90%) are diagnosed during the chronic stage which is most often asymptomatic. In these cases it may be diagnosed incidentally with an elevated white blood cell count on a routine laboratory test. It can also present with symptoms indicative of hepatosplenomegaly and the resulting upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.

Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.

Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis.

Chronic myelogenous leukemia (CML) is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood. CML is a clonal bone marrow stem cell disorder in which a proliferation of mature granulocytes (neutrophils, eosinophils and basophils) and their precursors is found. It is a type of myeloproliferative neoplasm associated with a characteristic chromosomal translocation called the Philadelphia chromosome.

CML is largely treated with targeted drugs called tyrosine-kinase inhibitors (TKIs) which have led to dramatic improved long-term survival rates since 2001. These drugs have revolutionized treatment of this disease and allow most patients to have a good quality of life when compared to the former chemotherapy drugs. In Western countries, CML accounts for 15–25% of all adult leukemias and 14% of leukemias overall (including the pediatric population, where CML is less common).

In humans, eosinophilic granulomas are considered a benign histiocytosis that occurs mainly in adolescents and young adults. Clinically, unifocal lytic lesions are found in bones such as the skull, ribs and femur. Because of this, bone pain and pathologic fractures are common.

Aside from the mosquito allergy cat, cats with EGC usually have allergy, ectoparasite infestation or possibly ringworm or other skin infection. Other implicated causes include traumatic damage, autoimmune disease or FeLV infection.

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.

A "left shift" refers to the presence of increased proportions of younger, less well differentiated neutrophils and neutrophil-precursor cells in the blood. This generally reflects early or premature release of myeloid cells from the bone marrow, the site where neutrophils are generated. A severe neutrophilia with left shift is referred to as a leukemoid reaction. The leukocyte alkaline phosphatase (LAP) score, which refers to the amount of alkaline phosphatase per neutrophil, will increase. In a severe infection, toxic granulation changes happen to the neutrophils.

This can resemble Pelger-Huet anomaly.

A foreign-body giant cell is a collection of fused macrophages (giant cell) which are generated in response to the presence of a large foreign body. This is particularly evident with implants that cause the body chronic inflammation and foreign body response.

This reaction to the implant causes damages to the infected area, leaving the exterior surface with scars.

The nuclei are arranged in a disorganized manner. The nuclei in this cell are centrally placed and overlap each other. This is in contrast to a Langhans giant cell, where the nuclei are arranged on the border.

Foreign body cells can detect and eliminate

bacteria caught within the body, by sensing the unique sugar coating that are

on the invading prokaryotes. These macrophage cells are one of a few

phagocytic cells, but not the first to come to an injury site, and tend to

linger from anytime between days to weeks. There has been some research done on other variations of

giant calls with different functions.

Small image of an infected area of the body due to a reaction with an implant

Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids.

For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present.

The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from bone marrow storage pools, decreased margination of leukocytes onto vessel walls, decreased extravasation of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.

Certain medications, including corticosteroids, lithium and beta agonists, may cause leukocytosis.

Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which neutrophils are elevated is neutrophilia; leukocytosis in which lymphocyte count is elevated is lymphocytosis; leukocytosis in which monocyte count is elevated is monocytosis; and leukocytosis in which eosinophil count is elevated is eosinophilia.

An extreme form of leukocytosis, in which the WBC count exceeds 100,000/µL, is leukostasis. In this form there are so many WBCs that clumps of them block blood flow. This leads to ischemic problems including transient ischemic attack and stroke.

Vitamin K reactions occur after injection with vitamin K, and there are two patterns of presentation, (1) a reaction may occur several days to 2 weeks after inection with skin lesions that are pruritic, red patches and plaques that can deep-seated, involving the dermis and subcutaneous tissue, or (2) with subcutaneous sclerosis with or without fasciitis, that appears at the site of injection many months after treatment. The latter pseudosclerodermatous reaction has been termed Texier's disease and lasts several years.

Shwartzman phenomenon, also known as Shwartzman reaction, is a rare reaction of a body to particular types of toxins, called endotoxins, which cause thrombosis in the affected tissue. A clearing of the thrombosis results in a reticuloendothelial blockade, which prevents re-clearing of the thrombosis caused by a repeat introduction of the toxin. That will cause tissue necrosis. Shwartzman phenomenon is usually observed during delivery or abortion, when foreign bodies are introduced into the tissues of the female reproductive system.

The Shwartzman phenomenon is named for Gregory Shwartzman, the doctor at Mount Sinai Hospital in New York City who was the first to develop the concept of immune system hypersensitivity in the 1920s.

This reaction was experimented using "Neisseria meningitidis" endotoxin.

This is notably seen with "Neisseria meningitidis".

It resembles bacterial sepsis and can occur after initiation of antibacterials, such as mild silver protein, penicillin or tetracycline, for the treatment of louse-borne relapsing fever (80–90% of patients) and in tick-borne relapsing fever (30–40%). It usually manifests within a few hours of the first dose of antibiotic as fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia (muscle pain), exacerbation of skin lesions and anxiety. The intensity of the reaction indicates the severity of inflammation. Reaction commonly occurs within two hours of drug administration, but is usually self-limiting. It is observed in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis.

Many conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment. The skin weighs an average of four kilograms, covers an area of two square meters, and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are: glabrous skin, the hairless skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, the hairs occur in structures called pilosebaceous units, each with hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands form from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues.

The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers by diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95 percent of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum.

The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing.

The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source.

Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying etiologies and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), etiology (skin conditions resulting from physical factors), and so on. Clinically, the diagnosis of any particular skin condition is made by gathering pertinent information regarding the presenting skin lesion(s), including the location (such as arms, head, legs), symptoms (pruritus, pain), duration (acute or chronic), arrangement (solitary, generalized, annular, linear), morphology (macules, papules, vesicles), and color (red, blue, brown, black, white, yellow). Diagnosis of many conditions often also requires a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data.

In immunology, the Arthus reaction (, ) is a type of local type III hypersensitivity reaction. Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli. This reaction is usually encountered in experimental settings following the injection of antigens.

Anticonvulsant/sulfonamide hypersensitivity syndrome is a potentially serious hypersensitivity reaction that can be seen with drugs with an aromatic amine chemical structure, such as aromatic anticonvulsants (e.g. diphenylhydantoin, phenobarbital, phenytoin, carbamazepine, lamotrigine), sulfonamides, or other drugs with an aromatic amine (procainamide). Cross-reactivity should not occur between drugs with an aromatic amine and drugs without an aromatic amine (e.g., sulfonylureas, thiazide diuretics, furosemide, and acetazolamide); therefore, these drugs can be safely used in the future.

The hypersensitivity syndrome is characterized by a skin eruption that is initially morbilliform. The rash may also be a severe Stevens-Johnson syndrome or toxic epidermal necrolysis. Systemic manifestations occur at the time of skin manifestations and include eosinophilia, hepatitis, and interstitial nephritis. However, a subgroup of patients may become hypothyroid as part of an autoimmune thyroiditis up to 2 months after the initiation of symptoms.

This kind of adverse drug reaction is caused by the accumulation of toxic metabolites; it is not the result of an IgE-mediated reaction. The risk of first-degree relatives’ developing the same hypersensitivity reaction is higher than in the general population.

As this syndrome can present secondary to multiple anticonvulsants, the general term "anticonvulsant hypersensitivity syndrome" is favored over the original descriptive term "dilantin hypersensitivity syndrome."

The Mazzotti reaction, first described in 1948, is a symptom complex seen in patients after undergoing treatment of onchocerciasis with the medication diethylcarbamazine (DEC). Mazzotti reactions can be life-threatening, and are characterized by fever, urticaria, swollen and tender lymph nodes, tachycardia, hypotension, arthralgias, oedema, and abdominal pain that occur within seven days of treatment of microfilariasis. The Mazzotti reaction correlates with intensity of infection; however, there are probably multiple infection intensity-dependent mechanisms responsible for mediating this complex reaction.

The phenomenon is so common when DEC is used for the treatment of onchocerciasis that this drug is the basis of a skin patch test used to confirm that diagnosis. The drug patch is placed on the skin, and if the patient is infected with the microfilaria of "O. volvulus", localized pruritus and urticaria are seen at the application site.

A case of the Mazzotti reaction has been reported after presumptive treatment of schistosomiasis and strongyloidiasis with ivermectin, praziquantel and albendazole. The patient had complete resolution of symptoms after intravenous therapy with methylprednisolone.

A Jarisch–Herxheimer reaction () is a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. Efficacious antimicrobial therapy results in lysis (destruction) of bacterial cell membranes, and in the consequent release into the bloodstream of bacterial toxins, resulting in a systemic inflammatory response.

Jarisch–Herxheimer reactions are usually not life-threatening.

Symptoms can take as long as 14 days after exposure to appear, and may include signs and symptoms commonly associated with hypersensitivity or infections.

- rashes

- itching

- joint pain (arthralgia), especially finger and toe joints

- fever, as high as 40 °C and usually appears before rash

- lymphadenopathy (swelling of lymph nodes), particularly near the site of injection, head and neck

- malaise

- hypotension (decreased blood pressure)

- splenomegaly (enlarged spleen)

- glomerulonephritis

- proteinuria

- hematuria

- shock

Generally, the areas affected are exposed skin not usually protected by clothing; however it can also occur in areas covered by clothing. Areas constantly subjected to the sun's rays may only be slightly affected if at all. People with extreme cases will also have reactions to light bulbs that emit a UV wavelength (any bulb that is not an LED). Parts of the body only thinly covered can also potentially be subjected to an outbreak.

Life with SU can be difficult. Patients are subject to constant itching and pain, as within minutes of the initial exposure to UV radiation a rash will appear. The urticarial reaction begins in the form of pruritus, later progressing to erythema and edema in the exposed areas of the skin. If vast areas of the body are affected, the loss of fluid into the skin could lead to light-headedness, headache, nausea, and vomiting. Extremely rarely, patients have been reported to experience an increase in heart rate that can cause a stroke or heart attack due to the body cavity swelling. Other rare side effects can be bronchospasm and glucose instability issues. Also, if a large area of the body is suddenly exposed the person may be subject to an anaphylactic reaction. Once free of exposure, the rash will usually fade away within several hours; rare and extreme cases can take a day or two to normalize depending on severity of the reaction.

Polymorphous light eruption (PMLE) is the easiest disease to mistake for solar urticaria because the locations of the lesions are similar (the V of the neck and the arms). However, patients with SU are more likely to develop lesions on the face. Also, a reaction with PMLE will take a greater amount of time to appear than with solar urticaria. Lupus erythematosus has been mistaken for SU; however, lesions from lupus erythematosus will take a longer amount of time to go away. Furthermore, when being tested for the two diseases, patients with SU have a reaction immediately while patients with lupus erythematosus will have a delayed reaction. Patients who have experienced solar urticarial symptoms from a young age could mistakenly be thought to have erythropoietic protoporphyria. However, the main symptom for this disease is pain and patients with have been found to have abnormal levels of protoporphyrin in their blood while these levels are normal in SU patients. Finally, cholinergic urticaria, or urticaria induced by heat, can occasionally appear to be solar urticaria because the heat from the sun will cause a person with the disease to have a reaction.

Diagnosis is based on history given by patient, including recent medications.

Bullous drug reaction (also known as a "bullous drug eruption", "generalized bullous fixed drug eruption", and "multilocular bullous fixed drug eruption") most commonly refers to a drug reaction in the erythema multiforme group. These are uncommon reactions to medications, with an incidence of 0.4 to 1.2 per million person-years for toxic epidermal necrolysis and 1.2 to 6.0 per million person-years for Stevens–Johnson syndrome. The primary skin lesions are large erythemas (faintly discernible even after confluence), most often irregularly distributed and of a characteristic purplish-livid color, at times with flaccid blisters.