Heavy chain diseases are conditions where the B-cells grow abnormally. These cells make faulty heavy chains of immunoglobulins, without the matching light chains. Gene changes like mutations, deletions, or insertions cause these abnormal proteins. The type of heavy chain disease depends on the class of immunoglobulin involved, with alpha (IgA), gamma (IgG), and mu (IgM) being most common. Alpha heavy chain disease often presents as a lymphoma of the mucosa associated lymphoid tissue. Mu heavy chain disease resembles small cell lymphoma or chronic lymphocytic leukemia. Gamma heavy chain disease has varying appearances and may differ from lymphoplasmacytoid lymphoma. Alpha heavy chain disease frequently affects young adults, particularly those of Arab or Jewish population from the Mediterranean or Middle East regions. Gamma heavy chain disease, also known as Franklin disease, more commonly affects middle aged individuals and has around 130 reported cases globally.
Epidemiology
Some key facts about a rare condition called Îł-HCD:
There are around 130 reported cases in the United States, making it an extremely uncommon disease. People of different races like Black, Asian, and White can get Îł-HCD. Males are a bit more likely than females to have this disorder. The age range when Îł-HCD is usually diagnosed is 42 to 87 years old, with most cases around 68 years.
Anatomy
Pathophysiology
In gamma heavy chain disease (Îł-HCD), an abnormal cell group called lymphoplasmacytoid makes an odd IgG protein. The changes in these cells have mutations, deletions, or insertions that affect both the constant and variable regions. They usually change the variable and constant parts of the protein. In one type, the hinge part stays the same. In another type, the change includes the hinge part. In both cases, the resulting protein is shorter than normal and tends to form polymers. The synthesis of light chains is down-regulated, suggesting either a 2-gene defect or a negative feedback effect.
Etiology
The exact cause of gamma-heavy chain disease is not known. Almost 25% of people have an autoimmune disorder such as:
Sjogren syndrome
Myasthenia gravis
Rheumatoid arthritis
SLE (systemic lupus erythematosus)
Autoimmune cytopenias such as immune thrombocytopenia
Genetics
Prognostic Factors
The prognosis for people with Îł-heavy chain disease (Îł-HCD) is not good. People with Îł-HCD suffer from infections of the upper respiratory tract. This is because their body’s defence system does not work well makes it hard to clear germs from their airways. Swelling in their mouth and throat areas makes it hard to cough up germs. Most people with Îł-HCD end up dying from bacterial infections.
People with Îł-HCD can get low red blood cell counts. Sometimes it is due to hemolytic anemia that is autoimmune. Other times it is from having a chronic illness. Like multiple myeloma, Îł-HCD can make holes in bones that lead to broken bones in the legs, back, and other areas.
Clinical History
About 25% of people with Îł-heavy chain disease (HCD) suffer from a localized disease in their body. But two-thirds of people with HCD have it spread out in many parts, including in the bone marrow and other areas. People with HCD have symptoms like a lymphoma. They may have swollen lymph nodes (lymphadenopathy), a swollen spleen (splenomegaly), and a swollen liver (hepatomegaly). They often feel weak, tired, and suffer from infrequent fevers. Around 60% of people with HCD have a swollen liver and spleen. As HCD gets worse, people get more swollen lymph nodes in their neck, armpits, chest, and belly areas.
Physical Examination
The period of gamma-HCD differs from presence of nonprogressive heavy chain (monoclonal) in urine or serum that might resolve spontaneously. A low percentage of Îł-HCD cases undergo MGUS (monoclonal gammopathy of undetermined significance). Signs and symptoms differ, and they include:
Fevers that sometimes resemble lymphoproliferative disorders.
Next to progressive lymphadenopathy of Waldeyer ring, oedema of soft palate leads to dysphagia.
Malaise can be considered as the secondary state of the disease.
Due to splenomegaly, pain in the abdomen may occur.
Frequent infection of the upper respiratory tract may occur due to altered cellular and humoral immunity.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
CLL (chronic lymphocytic leukemia)
B-Cell lymphoma
α-Heavy chain disease
Mu heavy chain disease
MGUS (monoclonal gammopathy of undetermined significance)
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Diagnosis and evaluation: Care must be taken in observing for symptoms of gamma-HCD in asymptomatic patients possessing low levels of serum IgG.
Medical care: Palliative care is of prime importance in the management of this condition. Chemotherapy involves the use of agents that are effective against multiple myeloma and lymphoma such as prednisone, doxorubicin, vincristine, chlorambucil, cyclophosphamide etc.
Though there is no clinical evidence, IVIg (intravenous immunoglobulin) is administered selectively to patients suffering from severe hypogammaglobulinemia.
Management of complications: Antibiotics should be administered for infections. Care should be taken in treating hemolytic anemia, autoimmune disorders and others that are complication specific. Surgical debulking or splenectomy may be rarely essential in cases of massive and symptomatic lymphadenopathy.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
modification-of-the-environment
Avoidance of immunogenic stimuli: People with gamma heavy chain disease must stay away from things that could make their immune system very active. This means avoiding infections, toxins from the environment, and things they are allergic to. These things can cause the body to make too many abnormal gamma heavy chains.
Infection control measures: It is very important to stop germs from spreading. This can make the disease worse. Steps must be followed to control infections. Washing hands often is a good way to stop germs. Staying away from infected people also prevents contracting the diseasae.
Nutritional support: Eating well is key to staying strong and healthy. People with gamma-HCD may need help from a nutrition expert. Taking extra vitamins and minerals may also be good. This helps make sure the body gets the required nutrients to fight against the conditions.
Psychological support: Having a rare disease like gamma-HCD can make life difficult. It is important to get help dealing with feelings. This can include talking to a counsellor, joining a support group, and learning ways to cope up. Support helps people feel better overall.
Use of antineoplastic agents
Fludarabine: It is an analogue of purine which interferes with the synthesis of DNA strands via inhibition of ribonucleotide reductase. It also causes the inhibition of RNA, synthesis of protein through incorporation into the RNA.
Rituximab: It is a human monoclonal antibody that is genetically prepared and directed to act against CD20 antigen which is found on the malignant and normal B lymphocytes.
Vincristine: this drug inhibits the mitosis by obstructing cells in metaphase of cell division.
Doxorubicin: It is an antimicrobial compound belonging to the class of anthracyclines. It is isolated from streptomyces, and it causes the cleavage of topoisomerase- II-dependent DNA and intercalates with the double helix of DNA.
Chlorambucil: It belongs to the class of nitrogen-mustard alkylating agents and used for treating Waldenstrom macroglobulinemia, chronic lymphocytic leukemia and as a 2nd and 3rd line of treatment for lymphomas. It inhibits the replication of DNA and transcription of RNA by alkylating the cross-links of DNA strands.
Use of corticosteroids
Prednisone: It inhibits the synthesis of mRNA and causes the breakdown of lymphoid tumors. Death of cells occurs because of fragmentation of cell.
phases-of-management
Diagnostic phase: A review of the medical history should be done followed by thorough physical examination to assess the signs and symptoms of the disease. Laboratory tests such as SPEP (serum protein electrophoresis), IFE (immunofixation electrophoresis) and bone marrow biopsy play a crucial role in confirming the diagnosis of Îł-HCD.
Treatment phase: This includes treating with various chemotherapy agents such as doxorubicin, cyclophosphamide, vincristine etc. Drugs such as rituximab target B-cell surface antigen CD20 to reduce the levels of abnormal B cells. Stem cell transplantation can also be considered as a curative treatment option.
Monitoring phase: After initiation of treatment, regular monitoring and follow-up visits are important to check the response on the patient to treatment and check for any side effects.
Heavy chain diseases are conditions where the B-cells grow abnormally. These cells make faulty heavy chains of immunoglobulins, without the matching light chains. Gene changes like mutations, deletions, or insertions cause these abnormal proteins. The type of heavy chain disease depends on the class of immunoglobulin involved, with alpha (IgA), gamma (IgG), and mu (IgM) being most common. Alpha heavy chain disease often presents as a lymphoma of the mucosa associated lymphoid tissue. Mu heavy chain disease resembles small cell lymphoma or chronic lymphocytic leukemia. Gamma heavy chain disease has varying appearances and may differ from lymphoplasmacytoid lymphoma. Alpha heavy chain disease frequently affects young adults, particularly those of Arab or Jewish population from the Mediterranean or Middle East regions. Gamma heavy chain disease, also known as Franklin disease, more commonly affects middle aged individuals and has around 130 reported cases globally.
Some key facts about a rare condition called Îł-HCD:
There are around 130 reported cases in the United States, making it an extremely uncommon disease. People of different races like Black, Asian, and White can get Îł-HCD. Males are a bit more likely than females to have this disorder. The age range when Îł-HCD is usually diagnosed is 42 to 87 years old, with most cases around 68 years.
In gamma heavy chain disease (Îł-HCD), an abnormal cell group called lymphoplasmacytoid makes an odd IgG protein. The changes in these cells have mutations, deletions, or insertions that affect both the constant and variable regions. They usually change the variable and constant parts of the protein. In one type, the hinge part stays the same. In another type, the change includes the hinge part. In both cases, the resulting protein is shorter than normal and tends to form polymers. The synthesis of light chains is down-regulated, suggesting either a 2-gene defect or a negative feedback effect.
The exact cause of gamma-heavy chain disease is not known. Almost 25% of people have an autoimmune disorder such as:
Sjogren syndrome
Myasthenia gravis
Rheumatoid arthritis
SLE (systemic lupus erythematosus)
Autoimmune cytopenias such as immune thrombocytopenia
The prognosis for people with Îł-heavy chain disease (Îł-HCD) is not good. People with Îł-HCD suffer from infections of the upper respiratory tract. This is because their body’s defence system does not work well makes it hard to clear germs from their airways. Swelling in their mouth and throat areas makes it hard to cough up germs. Most people with Îł-HCD end up dying from bacterial infections.
People with Îł-HCD can get low red blood cell counts. Sometimes it is due to hemolytic anemia that is autoimmune. Other times it is from having a chronic illness. Like multiple myeloma, Îł-HCD can make holes in bones that lead to broken bones in the legs, back, and other areas.
About 25% of people with Îł-heavy chain disease (HCD) suffer from a localized disease in their body. But two-thirds of people with HCD have it spread out in many parts, including in the bone marrow and other areas. People with HCD have symptoms like a lymphoma. They may have swollen lymph nodes (lymphadenopathy), a swollen spleen (splenomegaly), and a swollen liver (hepatomegaly). They often feel weak, tired, and suffer from infrequent fevers. Around 60% of people with HCD have a swollen liver and spleen. As HCD gets worse, people get more swollen lymph nodes in their neck, armpits, chest, and belly areas.
The period of gamma-HCD differs from presence of nonprogressive heavy chain (monoclonal) in urine or serum that might resolve spontaneously. A low percentage of Îł-HCD cases undergo MGUS (monoclonal gammopathy of undetermined significance). Signs and symptoms differ, and they include:
Fevers that sometimes resemble lymphoproliferative disorders.
Next to progressive lymphadenopathy of Waldeyer ring, oedema of soft palate leads to dysphagia.
Malaise can be considered as the secondary state of the disease.
Due to splenomegaly, pain in the abdomen may occur.
Frequent infection of the upper respiratory tract may occur due to altered cellular and humoral immunity.
CLL (chronic lymphocytic leukemia)
B-Cell lymphoma
α-Heavy chain disease
Mu heavy chain disease
MGUS (monoclonal gammopathy of undetermined significance)
Diagnosis and evaluation: Care must be taken in observing for symptoms of gamma-HCD in asymptomatic patients possessing low levels of serum IgG.
Medical care: Palliative care is of prime importance in the management of this condition. Chemotherapy involves the use of agents that are effective against multiple myeloma and lymphoma such as prednisone, doxorubicin, vincristine, chlorambucil, cyclophosphamide etc.
Though there is no clinical evidence, IVIg (intravenous immunoglobulin) is administered selectively to patients suffering from severe hypogammaglobulinemia.
Management of complications: Antibiotics should be administered for infections. Care should be taken in treating hemolytic anemia, autoimmune disorders and others that are complication specific. Surgical debulking or splenectomy may be rarely essential in cases of massive and symptomatic lymphadenopathy.
Hematology
Oncology, Other
Avoidance of immunogenic stimuli: People with gamma heavy chain disease must stay away from things that could make their immune system very active. This means avoiding infections, toxins from the environment, and things they are allergic to. These things can cause the body to make too many abnormal gamma heavy chains.
Infection control measures: It is very important to stop germs from spreading. This can make the disease worse. Steps must be followed to control infections. Washing hands often is a good way to stop germs. Staying away from infected people also prevents contracting the diseasae.
Nutritional support: Eating well is key to staying strong and healthy. People with gamma-HCD may need help from a nutrition expert. Taking extra vitamins and minerals may also be good. This helps make sure the body gets the required nutrients to fight against the conditions.
Psychological support: Having a rare disease like gamma-HCD can make life difficult. It is important to get help dealing with feelings. This can include talking to a counsellor, joining a support group, and learning ways to cope up. Support helps people feel better overall.
Hematology
Oncology, Other
Fludarabine: It is an analogue of purine which interferes with the synthesis of DNA strands via inhibition of ribonucleotide reductase. It also causes the inhibition of RNA, synthesis of protein through incorporation into the RNA.
Rituximab: It is a human monoclonal antibody that is genetically prepared and directed to act against CD20 antigen which is found on the malignant and normal B lymphocytes.
Vincristine: this drug inhibits the mitosis by obstructing cells in metaphase of cell division.
Doxorubicin: It is an antimicrobial compound belonging to the class of anthracyclines. It is isolated from streptomyces, and it causes the cleavage of topoisomerase- II-dependent DNA and intercalates with the double helix of DNA.
Chlorambucil: It belongs to the class of nitrogen-mustard alkylating agents and used for treating Waldenstrom macroglobulinemia, chronic lymphocytic leukemia and as a 2nd and 3rd line of treatment for lymphomas. It inhibits the replication of DNA and transcription of RNA by alkylating the cross-links of DNA strands.
Hematology
Oncology, Other
Prednisone: It inhibits the synthesis of mRNA and causes the breakdown of lymphoid tumors. Death of cells occurs because of fragmentation of cell.
Hematology
Oncology, Other
Diagnostic phase: A review of the medical history should be done followed by thorough physical examination to assess the signs and symptoms of the disease. Laboratory tests such as SPEP (serum protein electrophoresis), IFE (immunofixation electrophoresis) and bone marrow biopsy play a crucial role in confirming the diagnosis of Îł-HCD.
Treatment phase: This includes treating with various chemotherapy agents such as doxorubicin, cyclophosphamide, vincristine etc. Drugs such as rituximab target B-cell surface antigen CD20 to reduce the levels of abnormal B cells. Stem cell transplantation can also be considered as a curative treatment option.
Monitoring phase: After initiation of treatment, regular monitoring and follow-up visits are important to check the response on the patient to treatment and check for any side effects.
Heavy chain diseases are conditions where the B-cells grow abnormally. These cells make faulty heavy chains of immunoglobulins, without the matching light chains. Gene changes like mutations, deletions, or insertions cause these abnormal proteins. The type of heavy chain disease depends on the class of immunoglobulin involved, with alpha (IgA), gamma (IgG), and mu (IgM) being most common. Alpha heavy chain disease often presents as a lymphoma of the mucosa associated lymphoid tissue. Mu heavy chain disease resembles small cell lymphoma or chronic lymphocytic leukemia. Gamma heavy chain disease has varying appearances and may differ from lymphoplasmacytoid lymphoma. Alpha heavy chain disease frequently affects young adults, particularly those of Arab or Jewish population from the Mediterranean or Middle East regions. Gamma heavy chain disease, also known as Franklin disease, more commonly affects middle aged individuals and has around 130 reported cases globally.
Some key facts about a rare condition called Îł-HCD:
There are around 130 reported cases in the United States, making it an extremely uncommon disease. People of different races like Black, Asian, and White can get Îł-HCD. Males are a bit more likely than females to have this disorder. The age range when Îł-HCD is usually diagnosed is 42 to 87 years old, with most cases around 68 years.
In gamma heavy chain disease (Îł-HCD), an abnormal cell group called lymphoplasmacytoid makes an odd IgG protein. The changes in these cells have mutations, deletions, or insertions that affect both the constant and variable regions. They usually change the variable and constant parts of the protein. In one type, the hinge part stays the same. In another type, the change includes the hinge part. In both cases, the resulting protein is shorter than normal and tends to form polymers. The synthesis of light chains is down-regulated, suggesting either a 2-gene defect or a negative feedback effect.
The exact cause of gamma-heavy chain disease is not known. Almost 25% of people have an autoimmune disorder such as:
Sjogren syndrome
Myasthenia gravis
Rheumatoid arthritis
SLE (systemic lupus erythematosus)
Autoimmune cytopenias such as immune thrombocytopenia
The prognosis for people with Îł-heavy chain disease (Îł-HCD) is not good. People with Îł-HCD suffer from infections of the upper respiratory tract. This is because their body’s defence system does not work well makes it hard to clear germs from their airways. Swelling in their mouth and throat areas makes it hard to cough up germs. Most people with Îł-HCD end up dying from bacterial infections.
People with Îł-HCD can get low red blood cell counts. Sometimes it is due to hemolytic anemia that is autoimmune. Other times it is from having a chronic illness. Like multiple myeloma, Îł-HCD can make holes in bones that lead to broken bones in the legs, back, and other areas.
About 25% of people with Îł-heavy chain disease (HCD) suffer from a localized disease in their body. But two-thirds of people with HCD have it spread out in many parts, including in the bone marrow and other areas. People with HCD have symptoms like a lymphoma. They may have swollen lymph nodes (lymphadenopathy), a swollen spleen (splenomegaly), and a swollen liver (hepatomegaly). They often feel weak, tired, and suffer from infrequent fevers. Around 60% of people with HCD have a swollen liver and spleen. As HCD gets worse, people get more swollen lymph nodes in their neck, armpits, chest, and belly areas.
The period of gamma-HCD differs from presence of nonprogressive heavy chain (monoclonal) in urine or serum that might resolve spontaneously. A low percentage of Îł-HCD cases undergo MGUS (monoclonal gammopathy of undetermined significance). Signs and symptoms differ, and they include:
Fevers that sometimes resemble lymphoproliferative disorders.
Next to progressive lymphadenopathy of Waldeyer ring, oedema of soft palate leads to dysphagia.
Malaise can be considered as the secondary state of the disease.
Due to splenomegaly, pain in the abdomen may occur.
Frequent infection of the upper respiratory tract may occur due to altered cellular and humoral immunity.
CLL (chronic lymphocytic leukemia)
B-Cell lymphoma
α-Heavy chain disease
Mu heavy chain disease
MGUS (monoclonal gammopathy of undetermined significance)
Diagnosis and evaluation: Care must be taken in observing for symptoms of gamma-HCD in asymptomatic patients possessing low levels of serum IgG.
Medical care: Palliative care is of prime importance in the management of this condition. Chemotherapy involves the use of agents that are effective against multiple myeloma and lymphoma such as prednisone, doxorubicin, vincristine, chlorambucil, cyclophosphamide etc.
Though there is no clinical evidence, IVIg (intravenous immunoglobulin) is administered selectively to patients suffering from severe hypogammaglobulinemia.
Management of complications: Antibiotics should be administered for infections. Care should be taken in treating hemolytic anemia, autoimmune disorders and others that are complication specific. Surgical debulking or splenectomy may be rarely essential in cases of massive and symptomatic lymphadenopathy.
Hematology
Oncology, Other
Avoidance of immunogenic stimuli: People with gamma heavy chain disease must stay away from things that could make their immune system very active. This means avoiding infections, toxins from the environment, and things they are allergic to. These things can cause the body to make too many abnormal gamma heavy chains.
Infection control measures: It is very important to stop germs from spreading. This can make the disease worse. Steps must be followed to control infections. Washing hands often is a good way to stop germs. Staying away from infected people also prevents contracting the diseasae.
Nutritional support: Eating well is key to staying strong and healthy. People with gamma-HCD may need help from a nutrition expert. Taking extra vitamins and minerals may also be good. This helps make sure the body gets the required nutrients to fight against the conditions.
Psychological support: Having a rare disease like gamma-HCD can make life difficult. It is important to get help dealing with feelings. This can include talking to a counsellor, joining a support group, and learning ways to cope up. Support helps people feel better overall.
Hematology
Oncology, Other
Fludarabine: It is an analogue of purine which interferes with the synthesis of DNA strands via inhibition of ribonucleotide reductase. It also causes the inhibition of RNA, synthesis of protein through incorporation into the RNA.
Rituximab: It is a human monoclonal antibody that is genetically prepared and directed to act against CD20 antigen which is found on the malignant and normal B lymphocytes.
Vincristine: this drug inhibits the mitosis by obstructing cells in metaphase of cell division.
Doxorubicin: It is an antimicrobial compound belonging to the class of anthracyclines. It is isolated from streptomyces, and it causes the cleavage of topoisomerase- II-dependent DNA and intercalates with the double helix of DNA.
Chlorambucil: It belongs to the class of nitrogen-mustard alkylating agents and used for treating Waldenstrom macroglobulinemia, chronic lymphocytic leukemia and as a 2nd and 3rd line of treatment for lymphomas. It inhibits the replication of DNA and transcription of RNA by alkylating the cross-links of DNA strands.
Hematology
Oncology, Other
Prednisone: It inhibits the synthesis of mRNA and causes the breakdown of lymphoid tumors. Death of cells occurs because of fragmentation of cell.
Hematology
Oncology, Other
Diagnostic phase: A review of the medical history should be done followed by thorough physical examination to assess the signs and symptoms of the disease. Laboratory tests such as SPEP (serum protein electrophoresis), IFE (immunofixation electrophoresis) and bone marrow biopsy play a crucial role in confirming the diagnosis of Îł-HCD.
Treatment phase: This includes treating with various chemotherapy agents such as doxorubicin, cyclophosphamide, vincristine etc. Drugs such as rituximab target B-cell surface antigen CD20 to reduce the levels of abnormal B cells. Stem cell transplantation can also be considered as a curative treatment option.
Monitoring phase: After initiation of treatment, regular monitoring and follow-up visits are important to check the response on the patient to treatment and check for any side effects.
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