Autoinflammatory Periodic Fever Syndromes in Children
Ahmed Mohammed Hassan Al-brahmy;
Abstract
The periodic fever syndromes are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders, in which the disease is caused by abnormalities of the adaptive immune system, patients with autoinflammatory diseases do not produce autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the innate immune system (Masters et al., 2009).
The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system (Yel et al., 2013).
They include: familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency [MKD – previously known as hyperimmunoglobulin D (HIDS)], blau syndrome, deficiency of the interleukin (IL)-1-receptor antagonist (DIRA), pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPA syndrome), diseases of uncertain genetic aetiology including periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, the cryopyrin-associated periodic syndromes (CAPS) which include: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID) [also called chronic infantile neurological cutaneous and articular syndrome (CINCA)] (Lachmann, 2011).
The one clinical feature in common between all the periodic fever syndromes is the recurrent episodes of fever in the absence of infection, autoimmune disease or malignancy. The frequency of febrile attacks can vary between individuals and syndromes from daily to once every ten years. The duration of the fever during an attak may be hours or be virtually continuous, but is usually typical for a particular syndrome. The height of the fever may range from a slight elevation of temperature to over 40 degrees Celsius. The age at which the febrile attacks begin is also highly variable between the different syndromes with some beginning at or shortly after birth but others being delayed even as late as middle age.In some periodic fever syndromes there are well-recognised triggers for a febrile attack, such as generalized exposure to cold triggering a fever in FCAS. But in others no trigger is identified (De Sanctis et al., 2010).
Most periodic fever syndromes have associated symptoms and signs of inflammation at the same time as the fever. Commonly these affect the serosal surfaces, joints, eyes and skin. In some forms the predominant associated symptom is severe abdominal pain often leading to unnecessary exploratory surgery. In others, joint or neurological involvement can result in major disability. Quality of life can be severely impacted, particularly if febrile attacks are frequent or in those forms of periodic fever syndrome that develop joint or neurological complications. Secondary systemic amyloidosis develops in some periodic fever syndromes and this can result in life-threatening complications (Chauhan & Michet, 2014).
Table (7) list the most important distinguishing features of autoinflammatory symptoms.
Acute attacks of hereditary periodic fever syndromes are usually treated with bed rest, anti-inflammatory agents, analgesics and sometimes systemic corticosteroids. The fever does not respond to aspirin or paracetamol. Avoidance of triggers, where known, can reduce the frequency of attacks. Apart from colchicine for familial Mediterranean fever, treatment of the hereditary periodic fever syndromes is with biologic agents such as anakinra,given by subcutaneous injection. Treatment should be started as early as possible to prevent the development of life-threatening complications in such periodic fever syndromes (De Sanctis et al., 2010).
With increasing understanding of the genetics and pathophysiology of innate immunity and inflammation, the clinical concepts of periodic autoinflammatory fever syndromes may change. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients (Kastner and Goldbach, 2011).
The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system (Yel et al., 2013).
They include: familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency [MKD – previously known as hyperimmunoglobulin D (HIDS)], blau syndrome, deficiency of the interleukin (IL)-1-receptor antagonist (DIRA), pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPA syndrome), diseases of uncertain genetic aetiology including periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome, the cryopyrin-associated periodic syndromes (CAPS) which include: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease (NOMID) [also called chronic infantile neurological cutaneous and articular syndrome (CINCA)] (Lachmann, 2011).
The one clinical feature in common between all the periodic fever syndromes is the recurrent episodes of fever in the absence of infection, autoimmune disease or malignancy. The frequency of febrile attacks can vary between individuals and syndromes from daily to once every ten years. The duration of the fever during an attak may be hours or be virtually continuous, but is usually typical for a particular syndrome. The height of the fever may range from a slight elevation of temperature to over 40 degrees Celsius. The age at which the febrile attacks begin is also highly variable between the different syndromes with some beginning at or shortly after birth but others being delayed even as late as middle age.In some periodic fever syndromes there are well-recognised triggers for a febrile attack, such as generalized exposure to cold triggering a fever in FCAS. But in others no trigger is identified (De Sanctis et al., 2010).
Most periodic fever syndromes have associated symptoms and signs of inflammation at the same time as the fever. Commonly these affect the serosal surfaces, joints, eyes and skin. In some forms the predominant associated symptom is severe abdominal pain often leading to unnecessary exploratory surgery. In others, joint or neurological involvement can result in major disability. Quality of life can be severely impacted, particularly if febrile attacks are frequent or in those forms of periodic fever syndrome that develop joint or neurological complications. Secondary systemic amyloidosis develops in some periodic fever syndromes and this can result in life-threatening complications (Chauhan & Michet, 2014).
Table (7) list the most important distinguishing features of autoinflammatory symptoms.
Acute attacks of hereditary periodic fever syndromes are usually treated with bed rest, anti-inflammatory agents, analgesics and sometimes systemic corticosteroids. The fever does not respond to aspirin or paracetamol. Avoidance of triggers, where known, can reduce the frequency of attacks. Apart from colchicine for familial Mediterranean fever, treatment of the hereditary periodic fever syndromes is with biologic agents such as anakinra,given by subcutaneous injection. Treatment should be started as early as possible to prevent the development of life-threatening complications in such periodic fever syndromes (De Sanctis et al., 2010).
With increasing understanding of the genetics and pathophysiology of innate immunity and inflammation, the clinical concepts of periodic autoinflammatory fever syndromes may change. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients (Kastner and Goldbach, 2011).
Other data
| Title | Autoinflammatory Periodic Fever Syndromes in Children | Other Titles | متلازمات الحمى الدورية ذاتية الالتهاب في الأطفال | Authors | Ahmed Mohammed Hassan Al-brahmy | Issue Date | 2015 |
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