Introduction
Gamma heavy chain disease (HCD) is a rare variant of HCD, a family of syndromes associated with or constitutes B cell mutant malignancies. The characteristics and pathogenic mechanism of HCD are neither quaternary confirmation on the immunoglobulin light chain (IgL) nor degradation by the proteasome, synthesis of mutated and misfolded immunoglobulin heavy chains (IgH). The mutated IgH isotype (α γ, or μ) determines the terminology of the HCD subtype. Less than two hundred cases of Gamma HCD have been published. Gamma-HCD mainly affects women between the ages of 50s and 60s. About a quarter of patients have suffered from pre-existing autoimmune diseases for decades.
Rheumatoid arthritis (RA) is the most commonly associated autoimmune disease but is also associated with systemic lupus erythematosus (SLE), Sjogren's syndrome, severe myasthenia, vasculitis, and idiopathic thrombocytopenic purpura (ITP). The majority of patients with gamma HCD have localized or systemic lymphoma. Patients with gamma HCD may have no disseminated lymphoma lesions, localized (medullary or extramedullary), or overt lymphoma lesions. Disseminated lymphoma is the most common form diagnosed in 57 to 66 % of patients with gamma HCD. These patients usually present with symptoms such as fever, malaise, and unintentional weight loss.
What Is Gamma Heavy Chain Disease?
Gamma heavy chain disease (gHCD) is a plasma cell neoplasm characterized by the production and secretion of abnormally cleaved IgG chains that cannot bind to lymphocytes, plasma cell-like lymphocytes, and immunoglobulin light chains.
What Causes Gamma Heavy Chain Disease?
The occurrence of gamma HCD is unknown. Approximately 25 % of patients with gamma HCD have a history of autoimmune diseases such as
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Rheumatoid Arthritis - A chronic inflammatory disease that affects many joints, including the hands and feet.
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Sjogren's Syndrome - An immune system disorder characterized by dry eye and dry mouth (xerostomia).
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Systemic Lupus Erythematosus - An inflammatory disease that occurs when the immune system attacks its own tissues.
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Myasthenia Gravis - Muscle weakness and rapid fatigue under spontaneous control.
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Autoimmune Thrombocytopenia - A disorder in which the number of platelets in the blood is low.
What Are the Symptoms Seen With Gamma Heavy Chain Disease?
The signs and symptoms of gamma HCD vary; some common symptoms include:
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Fever recurs frequently and resembles lymphoproliferative disorders.
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Discomfort may be due to the condition itself or anemia. Mild anemia is widespread in patients with disseminated gamma-HCD.
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Dysphagia is usually caused by soft palate edema secondary to progressive lymphadenopathy of the Waldeyer ring. This edema can also cause pain in the tongue.
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Recurrent upper respiratory tract infections are caused by impaired humoral and cell-mediated immunity, but other factors may also contribute, such as lymphoid hyperplasia, which can reduce airway pathogen clearance.
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Abdominal pain may be present and is caused by splenomegaly, hepatomegaly, and abdominal lymphadenopathy.
How Is Gamma Heavy Chain Disease Diagnosed?
Gamma heavy chain diseases can be diagnosed with the help of the following tests and imaging:
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Complete blood count (CBC) can indicate mild normocytic anemia, which affects virtually all patients. Leukopenia and leukocytosis may be present, but WBC and differential cell counts are usually normal. Eosinophilia and thrombocytopenia can occur as a result of autoimmune processes or hypersplenism.
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Measuring creatinine levels is essential. This is because the renal function may be impaired due to nodular glomerulosclerosis caused by monoclonal heavy chain deposition. As a result, hyperuricemia is common in patients with advanced illnesses.
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Serum protein electrophoresis (SPE) is indicated. Monoclonal peaks with electrophoretic mobility in the alpha-gamma region are detected in approximately 75 % of patients.
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X-rays can show lytic bone lesions in about ten percent of patients. Osteoporosis is rare.
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Bone marrow biopsy with aspirates often increases the number of plasma cells, lymphocytes, and plasma cell-like lymphocytes, but the results may be average.
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Bone marrow biopsy with aspirates often increases the number of plasma cells, lymphocytes, and plasma cell-like lymphocytes, but the results may be average.
How Is Gamma Heavy Chain Disease Treated?
Treatment of gamma heavy chain disease should focus on palliative care, as disease management is disappointing.
1. Close observation is required in asymptomatic patients with low serum IgG levels and no signs of other diseases (appearances such as monoclonal immunoglobulin [MGUS] of unknown importance).
2. Chemotherapy with drugs primarily effective for lymphoma and multiple myeloma (such as Cyclophosphamide, Prednisone, Vincristine Chlorambucil, and Doxorubicin) was disappointing. However, partial and short-lived reactions with Fludarabine and Rituximab have been reported.
3. Intravenous immunoglobulin (IVIg) has been used in some patients with severe hypogammaglobulinemia, but no clinical studies support this practice. The treatments for complications are:
- Complication-specific management of autoimmune diseases, hemolytic anemia, and other diseases.
- Antibiotics for infectious diseases.
What Is the Prognosis for Gamma Heavy Chain Disease?
The prognosis for patients with γ-HCD is poor. The clinical course varies. Some patients remain asymptomatic for months or years. Others have a period of waxing and waning. In addition, some people experience a rapidly progressing course that dies within a few months of diagnosis.
Conclusion:
Gamma heavy chain disease disturbs the growth of cells in the immune system. People with this disease form irregular forms of heavy gamma chains, the proteins that produce antibodies. This abnormal protein is overproduced by the body and can cause abnormal cell proliferation. Gamma heavy chain disease mainly affects the elderly and has symptoms such as swollen lymph nodes, enlarged liver and spleen, and anemia. People with gamma heavy chain disease are asymptomatic; others have many symptoms and can develop malignant lymphoma. The cause of gamma heavy chain disease is unknown, but about one-third of people in this condition is autoimmune. Diagnosis is based on detecting high levels of heavy gamma chains in blood, urine, and bone marrow. Gamma heavy chain disease is one of three types of heavy chain disease.
