The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.

Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord).

In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.

While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.

An experimental treatment, an anti IFN-gamma monoclonal antibody tentatively named NI-0501, is in clinical trials for treating primary HLH. The FDA awarded breakthrough drug status to NI-0501 in 2016.

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.

Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency. T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away.

Griscelli syndrome type 2 (also known as "partial albinism with immunodeficiency") is a rare autosomal recessive syndrome characterized by variable pigmentary dilution, hair with silvery metallic sheen, frequent pyogenic infections, neutropenia, and thrombocytopenia.

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

X-linked lymphoproliferative disease (also known as "Duncan's disease" or "Purtilo syndrome") is a lymphoproliferative disorder.

Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.

Howel–Evans syndrome is an extremely rare condition involving thickening of the skin in the palms of the hands and the soles of the feet (hyperkeratosis). This familial disease is associated with a high lifetime risk of esophageal cancer. For this reason, it is sometimes known as tylosis with oesophageal cancer (TOC).

The condition is inherited in an autosomal dominant manner, and it has been linked to a mutation in the "RHBDF2" gene. It was first described in 1958.

Strangely, in boys with X-linked lymphoproliferative disorder, there is an inability to mount an immune response to the Epstein-Barr virus (EBV), which often leads to death from bone marrow failure, irreversible hepatitis, and malignant lymphoma. However, the connection between EBV and X-linked lymphoproliferative disorder is yet to be determined.

Patients produce insufficient numbers of CD27 memory B cells.

This condition is inherited as an autosomal dominant syndrome and characterized by palmoplantar keratoderma, oral precursor lesions particularly on the gums (leukoplakia) and a high lifetime risk of esophageal cancer (95% develop esophageal cancer by the age of 65). Relapsing cutaneous horns of the lips has been reported in this condition.

There are several types of this condition have been described – epidermolytic (Vörner type) and non-epidermolytic. Another classification divides these into an early onset type (type B) which occurs in the first year of life and is usually benign and a type A tylosis which occurs between the ages of 5 and 15 years and is strongly associated with esophageal cancer.

Cytoglobin gene expression in oesphageal biopsies is significantly reduced (70% reduction) in this condition. The mechanism of this change is not known.

The best treatment for MAS has not been firmly established. Most commonly used treatments include high-dose glucocorticoids, and cyclosporine. In refractory cases treatment regimens are used similar to that in HLH.

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

Prognosis depends greatly on the nature and severity of the condition. Some deficiencies cause early mortality (before age one), others with or even without treatment are lifelong conditions that cause little mortality or morbidity. Newer stem cell transplant technologies may lead to gene based treatments of

debilitating and fatal genetic immune deficiencies. Prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or

condition (like AIDS).

Most histiocytomas will regress within two or three months. Surgical removal may be necessary if the tumor does not regress or if it is growing rapidly to a large size. Histiocytomas should never be treated with an intralesional injection of a corticosteroid, as remission relies on recognition of the tumour by the body's immune system which is suppressed by steroids.

Wolf–Hirschhorn syndrome (WHS), also known as chromosome deletion Dillan 4p syndrome, Pitt–Rogers–Danks syndrome (PRDS) or Pitt syndrome, was first described in 1961 by Americans Herbert L. Cooper and Kurt Hirschhorn and, thereafter, gained worldwide attention by publications by the German Ulrich Wolf, and Hirschhorn and their co-workers, specifically their articles in the German scientific magazine "Humangenetik". It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome 4 (del(4p16.3)).

Malignant histiocytosis (also known as "Histiocytic medullary reticulosis") is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

Available treatment falls into two modalities: treating infections and boosting the immune system.

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.

Screening for melanoma in FAMMM kindreds should begin at age 10 with a baseline total body skin examination including scalp, eyes, oral mucosa, genital area, and nail, as family members may develop melanoma in their early teens.

At Mayo Clinic, FAMMM patients with a confirmed mutation and family history of pancreatic cancer are offered screening with either high-resolution pancreatic protocol CT, MRI, or endoscopic ultrasound starting at age 50 or 10 years younger than the earliest family member with pancreas cancer. They are counseled on the lack of evidence-based data to support screening, and on the limitations of our current technology to detect a lesion at a stage amenable to therapy.

This includes Chediak-Higashi syndrome and Elejalde syndrome (neuroectodermal melanolysosomal disease).

Hepatoerythropoietic porphyria is a very rare form of hepatic porphyria caused by a disorder in both genes which code Uroporphyrinogen III decarboxylase (UROD).

It has a similar presentation to porphyria cutanea tarda (PCT), but with earlier onset. In classifications which define PCT type 1 as "sporadic" and PCT type 2 as "familial", hepatoerythropoietic porphyria is more similar to type 2.

Treat the underlying cause

Blood transfusion (PRBC) according to need

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

In 1820 Norris reported the first case of what is now recognized as FAMMM (12). He described a 59-year-old man with melanoma, a high total body mole count, and family history of the same.