Avoidance of antitoxins that may cause serum sickness is the best way to prevent serum sickness. Although, sometimes, the benefits outweigh the risks in the case of a life-threatening bite or sting. Prophylactic antihistamines or corticosteroids may be used concomitant with the antitoxin. Skin testing may be done beforehand in order to identify individuals who may be at risk of a reaction. Physicians should make their patients aware of the drugs or antitoxins to which they are allergic if there is a reaction. The physician will then choose an alternate antitoxin if it's appropriate or continue with prophylactic measures.

With discontinuation of offending agent, symptoms usually disappear within 4–5 days.

Corticosteroids, antihistamines, and analgesics are the main line of treatment. The choice depends on the severity of the reaction.

Use of plasmapheresis has also been described.

In type II hypersensitivity (also tissue-specific, or cytotoxic hypersensitivity) the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. The antigens recognized in this way may either be intrinsic ("self" antigen, innately part of the patient's cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

An example of type II hypersensitivity is the ABO blood incompatibility where the red blood cells have different antigens, causing them to be recognized as different; B cell proliferation will take place and antibodies to the foreign blood type are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens. That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day.

Type II reactions can affect healthy cells. Examples include red blood cells in autoimmune hemolytic anemia and acetylcholine receptors in myasthenia gravis.

Another example of type II hypersensitivity reaction is Goodpasture's syndrome where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies.

Another form of type II hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer cells (NK) and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.

An example of a tuberculosis (TB) infection that comes under control: "M. tuberculosis" cells are engulfed by macrophages after being identified as foreign, but due to an immuno-escape mechanism peculiar to mycobacteria, TB bacteria are able to block the fusion of their enclosing phagosome with lysosomes which would destroy the bacteria. Thereby TB can continue to replicate within macrophages. After several weeks, the immune system somehow [mechanism as yet unexplained] ramps up and, on stimulation with IFN-gamma, the macrophages become capable of killing "M. tuberculosis" by forming phagolysosomes and nitric oxide radicals. The hyper-activated macrophages secrete TNF-α which recruits multiple monocytes to the site of infection. These cells differentiate into epithelioid cells which wall off the infected cells, but results in significant inflammation and local damage.

Some other clinical examples:

- Temporal arteritis

- Leprosy

- Coeliac disease

- Graft-versus-host disease

- Chronic transplant rejection

Type 4 hypersensitivity is often called delayed type hypersensitivity as the reaction takes several days to develop. Unlike the other types, it is not antibody-mediated but rather is a type of cell-mediated response.

CD4+ T1 helper T cells recognize antigen in a complex with the MHC class II major histocompatibility complex on the surface of antigen-presenting cells. These can be macrophages that secrete IL-12, which stimulates the proliferation of further CD4+ T1 cells. CD4+ T cells secrete IL-2 and interferon gamma, inducing the further release of other T1 cytokines, thus mediating the immune response. Activated CD8+ T cells destroy target cells on contact, whereas activated macrophages produce hydrolytic enzymes and, on presentation with certain intracellular pathogens, transform into multinucleated giant cells.

The preferred treatment for many patients is desensitization to aspirin, undertaken at a clinic or hospital specializing in such treatment. In the United States, the Scripps Clinic in San Diego, CA, the Massachusetts General Hospital in Boston, MA, the Brigham and Women's Hospital in Boston, MA, National Jewish Hospital in Denver and Stanford University Adult ENT Clinic have allergists who routinely perform aspirin desensitization procedures for patients with aspirin-induced asthma. Patients who are desensitized then take a maintenance dose of aspirin daily and while on daily aspirin they often have reduced need for supporting medications, fewer asthma and sinusitis symptoms than previously, and many have an improved sense of smell. Desensitization to aspirin reduces the chance of nasal polyp recurrence, and can slow the regrowth of nasal polyps. Even patients desensitized to aspirin may continue to need other medications including nasal steroids, inhaled steroids, and leukotriene antagonists.

Leukotriene antagonists and inhibitors (montelukast, zafirlukast, and zileuton) are often helpful in treating the symptoms of aspirin-induced asthma. Some patients require oral steroids to alleviate asthma and congestion, and most patients will have recurring or chronic sinusitis due to the nasal inflammation.

An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but evidence does not show effectiveness.

A review found no effectiveness of homeopathic treatments and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.

According to the NCCIH, the evidence is relatively strong that saline nasal irrigation and butterbur are effective, when compared to other alternative medicine treatments, for which the scientific evidence is weak, negative, or nonexistent, such as honey, acupuncture, omega 3's, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora or guduchi.

Allergen immunotherapy is useful for environmental allergies, allergies to insect bites, and asthma. Its benefit for food allergies is unclear and thus not recommended. Immunotherapy involves exposing people to larger and larger amounts of allergen in an effort to change the immune system's response.

Meta-analyses have found that injections of allergens under the skin is effective in the treatment in allergic rhinitis in children and in asthma. The benefits may last for years after treatment is stopped. It is generally safe and effective for allergic rhinitis and conjunctivitis, allergic forms of asthma, and stinging insects.

The evidence also supports the use of sublingual immunotherapy for rhinitis and asthma but it is less strong. For seasonal allergies the benefit is small. In this form the allergen is given under the tongue and people often prefer it to injections. Immunotherapy is not recommended as a stand-alone treatment for asthma.

Type III hypersensitivity occurs when there is an excess of antigen, leading to small immune complexes being formed that fix complement and are not cleared from the circulation. It involves soluble antigens that are not bound to cell surfaces (as opposed to those in type II hypersensitivity). When these antigens bind antibodies, immune complexes of different sizes form. Large complexes can be cleared by macrophages but macrophages have difficulty in the disposal of small immune complexes. These immune complexes insert themselves into small blood vessels, joints, and glomeruli, causing symptoms. Unlike the free variant, a small immune complex bound to sites of deposition (like blood vessel walls) are far more capable of interacting with complement; these medium-sized complexes, formed in the slight excess of antigen, are viewed as being highly pathogenic.

Such depositions in tissues often induce an inflammatory response, and can cause damage wherever they precipitate. The cause of damage is as a result of the action of cleaved complement anaphylotoxins C3a and C5a, which, respectively, mediate the induction of granule release from mast cells (from which histamine can cause urticaria), and recruitment of inflammatory cells into the tissue (mainly those with lysosomal action, leading to tissue damage through frustrated phagocytosis by PMNs and macrophages).

The reaction can take hours, days, or even weeks to develop, depending on whether or not there is immunological memory of the precipitating antigen. Typically, clinical features emerge a week following initial antigen challenge, when the deposited immune complexes can precipitate an inflammatory response. Because of the nature of the antibody aggregation, tissues that are associated with blood filtration at considerable osmotic and hydrostatic gradient (e.g. sites of urinary and synovial fluid formation, kidney glomeruli and joint tissues respectively) bear the brunt of the damage. Hence, vasculitis, glomerulonephritis and arthritis are commonly associated conditions as a result of type III hypersensitivity responses.

As observed under methods of histopathology, acute necrotizing vasculitis within the affected tissues is observed concomitant to neutrophilic infiltration, along with notable eosinophilic deposition (fibrinoid necrosis). Often, immunofluorescence microscopy can be used to visualize the immune complexes. Skin response to a hypersensitivity of this type is referred to as an Arthus reaction, and is characterized by local erythema and some induration. Platelet aggregation, especially in microvasculature, can cause localized clot formation, leading to blotchy hemorrhages. This typifies the response to injection of foreign antigen sufficient to lead to the condition of serum sickness.

Type III hypersensitivity occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes. Such reactions progressing to the point of disease produce immune complex diseases.

Often surgery is required to remove nasal polyps, although they typically recur, particularly if aspirin desensitization is not undertaken. 90% of patients have been shown to have recurrence of nasal polyps within 5 years after surgery, with 47% requiring revision surgery in the same time period.

The Xanthogranulomatous Process (XP), also known as Xanthogranulomatous Inflammation is a form of acute and chronic inflammation characterized by an exuberant clustering of foamy macrophages among other inflammatory cells. Localization in the kidney and renal pelvis has been the most frequent and better known occurrence followed by that in the gallbladder but many others have been subsequently recorded. The pathological findings of the process and etiopathogenetic and clinical observations have been reviewed by Cozzutto and Carbone.

Corticosteroids and other immunosuppressive medications have historically been employed to reduce pemphigus symptoms, yet steroids are associated with serious and long-lasting side effects and their use should be limited as much as possible. Intravenous immunoglobulin, mycophenolate mofetil, methotrexate, azathioprine, and cyclophosphamide have also been used with varying degrees of success.

An established alternative to steroids are monoclonal antibodies such as rituximab, which are increasingly being used as first-line treatment. In numerous case series, many patients achieve remission after one cycle of rituximab. Treatment is more successful if initiated early on in the course of disease, perhaps even at diagnosis. Rituximab treatment combined with monthly IV immunoglobulin infusions has resulted in long-term remission with no recurrence of disease in 10 years after treatment was halted. This was a small trial study of 11 patients with 10 patients followed to completion.

Underlying disease must be controlled to prevent exacerbation and worsening of ABPA, and in most patients this consists of managing their asthma or CF. Any other co-morbidities, such as sinusitis or rhinitis, should also be addressed.

Hypersensitivity mechanisms, as described above, contribute to progression of the disease over time and, when left untreated, result in extensive fibrosis of lung tissue. In order to reduce this, corticosteroid therapy is the mainstay of treatment (for example with prednisone); however, studies involving corticosteroids in ABPA are limited by small cohorts and are often not double-blinded. Despite this, there is evidence that acute-onset ABPA is improved by corticosteroid treatment as it reduces episodes of consolidation. There are challenges involved in long-term therapy with corticosteroids—which can induce severe immune dysfunction when used chronically, as well as metabolic disorders—and approaches have been developed to manage ABPA alongside potential adverse effects from corticosteroids.

The most commonly described technique, known as sparing, involves using an antifungal agent to clear spores from airways adjacent to corticosteroid therapy. The antifungal aspect aims to reduce fungal causes of bronchial inflammation, whilst also minimising the dose of corticosteroid required to reduce the immune system’s input to disease progression. The strongest evidence (double-blinded, randomized, placebo-controlled trials) is for itraconazole twice daily for four months, which resulted in significant clinical improvement compared to placebo, and was mirrored in CF patients. Using itraconazole appears to outweigh the risk from long-term and high-dose prednisone. Newer triazole drugs—such as posaconazole or voriconazole—have not yet been studied in-depth through clinical trials in this context.

Whilst the benefits of using corticosteroids in the short term are notable, and improve quality of life scores, there are cases of ABPA converting to invasive aspergillosis whilst undergoing corticosteroid treatment. Furthermore, in concurrent use with itraconazole, there is potential for drug interaction and the induction of Cushing syndrome in rare instances. Metabolic disorders, such as diabetes mellitus and osteoporosis, can also be induced.

In order to mitigate these risks, corticosteroid doses are decreased biweekly assuming no further progression of disease after each reduction. When no exacerbations from the disease are seen within three months after discontinuing corticosteroids, the patient is considered to be in complete remission. The exception to this rule is patients who are diagnosed with advanced ABPA; in this case removing corticosteroids almost always results in exacerbation and these patients are continued on low-dose corticosteroids (preferably on an alternate-day schedule).

Serum IgE can be used to guide treatment, and levels are checked every 6–8 week after steroid treatment commences, followed by every 8 weeks for one year. This allows for determination of baseline IgE levels, though it’s important to note that most patients do not entirely reduce IgE levels to baseline. Chest X-ray or CT scans are performed after 1–2 months of treatment to ensure infiltrates are resolving.

Corticosteroids: For years, there was no treatment for atopic eczema. Atopy was believed to be allergic in origin due to the patients’ extremely high serum IgE levels, but standard therapies at the time did not help. Oral prednisone was sometimes prescribed for severe cases. Wet wraps (covering the patients with gauze) were sometimes used in hospitals to control itching. However, the discovery of corticosteroids in the 1950s, and their subsequent incorporation in topical creams and ointments, provided a significant advancement in the treatment of atopic eczema and other conditions. Thus, the use of topical steroids avoided many of the undesirable side-effects of systemic administration of corticosteroids. Topical steroids control the itching and the rash that accompany atopic eczema. Side-effects of topical steroid use are plentiful, and the patient is advised to use topical steroids in moderation and only as needed.

Immune modulators: Pimecrolimus and tacrolimus creams and ointments became available in the 1980s and are sometimes prescribed for atopic eczema. They act by interfering with T cells but have been linked to the development of cancer.

Avoiding dry skin: Dry skin is a common feature of patients with atopic eczema (see also eczema for information) and can exacerbate atopic eczema.

Avoiding allergens and irritants: See eczema for information.

Treatment usually involves adrenaline (epinephrine), antihistamines, and corticosteroids.

If the entire body is involved, then anaphylaxis can take place, which is an acute, systemic reaction that can prove fatal.

The Arthus reaction involves the in situ formation of antigen/antibody complexes after the intradermal injection of an antigen. If the animal/patient was previously sensitized (has circulating antibody), an Arthus reaction occurs. Typical of most mechanisms of the type III hypersensitivity, Arthus manifests as local vasculitis due to deposition of IgG-based immune complexes in dermal blood vessels. Activation of complement primarily results in cleavage of soluble complement proteins forming C5a and C3a, which activate recruitment of PMNs and local mast cell degranulation (requiring the binding of the immune complex onto FcγRIII), resulting in an inflammatory response. Further aggregation of immune complex-related processes induce a local fibrinoid necrosis with ischemia-aggravating thrombosis in the tissue vessel walls. The end result is a localized area of redness and induration that typically lasts a day or so.

Arthus reactions have been infrequently reported after vaccinations containing diphtheria and tetanus toxoid. The CDC's description:

Arthus reactions (type III hypersensitivity reactions) are rarely reported after vaccination and can occur after tetanus toxoid–containing or diphtheria toxoid–containing vaccines. An Arthus reaction is a local vasculitis associated with deposition of immune complexes and activation of complement. Immune complexes form in the setting of high local concentration of vaccine antigens and high circulating antibody concentration. Arthus reactions are characterized by severe pain, swelling, induration, edema, hemorrhage, and occasionally by necrosis. These symptoms and signs usually occur 4–12 hours after vaccination. ACIP has recommended that persons who experienced an Arthus reaction after a dose of tetanus toxoid–containing vaccine should not receive Td more frequently than every 10 years, even for tetanus prophylaxis as part of wound management.

Xanthogranulomatous osteomyelitis (XO) is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.

The culprit can be both a prescription drug or an over-the-counter medication.

Examples of common drugs causing drug eruptions are antibiotics and other antimicrobial drugs, sulfa drugs, nonsteroidal anti-inflammatory drugs (NSAIDs), biopharmaceuticals, chemotherapy agents, anticonvulsants, and psychotropic drugs. Common examples include photodermatitis due to local NSAIDs (such as piroxicam) or due to antibiotics (such as minocycline), fixed drug eruption due to acetaminophen or NSAIDs (Ibuprofen), and the rash following ampicillin in cases of mononucleosis.

Certain drugs are less likely to cause drug eruptions (rates estimated to be ≤3 per 1000 patients exposed). These include: digoxin, aluminum hydroxide, multivitamins, acetaminophen, bisacodyl, aspirin, thiamine, prednisone, atropine, codeine, hydrochlorothiazide, morphine, insulin, warfarin, and spironolactone.

The Arthus reaction was discovered by Nicolas Maurice Arthus in 1903. Arthus repeatedly injected horse serum subcutaneously into rabbits. After four injections, he found that there was edema and that the serum was absorbed slowly. Further injections eventually led to gangrene.

Research into using genetically modified T-cells to treat pemphigus vulgaris in mice was reported in 2016. Rituximab indiscriminately attacks all B cells, which reduces the body's ability to control infections. In the experimental treatment, human T cells are genetically engineered to recognize only those B cells that produce antibodies to desmoglein 3.

In many cases, MHA requires no treatment. However, in extreme cases, blood platelet transfusions may be necessary

Antiviral treatment has been tried with some success in a small number of patients.

The T helper cells (T cells) are a type of T cell that play an important role in the immune system, particularly in the adaptive immune system. They help the activity of other immune cells by releasing T cell cytokines. These cells help suppress or regulate immune responses. They are essential in B cell antibody class switching, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages.

Mature T cells express the surface protein CD4 and are referred to as CD4 T cells. Such CD4 T cells are generally treated as having a pre-defined role as helper T cells within the immune system. For example, when an antigen-presenting cell expresses an antigen on MHC class II, a CD4 cell will aid those cells through a combination of cell to cell interactions (e.g. CD40 (protein) and CD40L) and through cytokines.

CD154, also called CD40 ligand or CD40L, is a cell surface protein that mediates T cell helper function in a contact-dependent process and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells (APC), which leads to many effects depending on the target cell type. CD154 acts as a costimulatory molecule and is particularly important on a subset of T cells called T follicular helper cells (T cells). On T cells, CD154 promotes B cell maturation and function by engaging CD40 on the B cell surface and therefore facilitating cell-cell communication. A defect in this gene results in an inability to undergo immunoglobulin class switching and is associated with hyper IgM syndrome. Absence of CD154 also stops the formation of germinal centers and therefore prohibiting antibody affinity maturation, an important process in the adaptive immune system.

The importance of helper T cells can be seen from HIV, a virus that primarily infects CD4 T cells. In the advanced stages of HIV infection, loss of functional CD4 T cells leads to the symptomatic stage of infection known as the acquired immunodeficiency syndrome (AIDS). When the HIV virus is detected early in blood or other bodily fluids, continuous therapy can delay the time at which this fall happens. Therapy can also better manage the course of AIDS if and when it occurs. There are other rare disorders such as lymphocytopenia which result in the absence or dysfunction of CD4 T cells. These disorders produce similar symptoms, many of which are fatal.

Throughout the years, many different treatments have been tried for morphea including topical, intra-lesional, and systemic corticosteroids. Antimalarials such as hydroxychloroquine or chloroquine have been used. Other immunomodulators such as methotrexate, topical tacrolimus, and penicillamine have been tried. Some have tried prescription vitamian-D with success. Ultraviolet A (UVA) light, with or without psoralens have also been tried. UVA-1, a more specific wavelength of UVA light, is able to penetrate the deeper portions of the skin and thus, thought to soften the plaques in morphea by acting in two fashions:

- 1) by causing a systemic immunosuppression from UV light.

- 2) by inducing enzymes that naturally degrade the collagen matrix in the skin as part of natural sun-aging of the skin.

As with all of these treatments for morphea, the difficulty in assessing outcomes in an objective way has limited the interpretation of most studies involving these treatment modalities.