Rare diseases are serious, often chronic and progressive conditions. There are thousands of these rare diseases. To date, six to seven thousand rare diseases have been discovered. New diseases are regularly described in the medical literature. The number of rare diseases also depends on the degree of specificity used in classifying the different presentations/disorders. To date, a disease has been defined in medicine as a change in health status that presents as a unique pattern of symptoms with a single treatment. Whether a pattern is considered unique depends entirely on the level of definition of our analysis.
In many rare disorders, such as hemophilia or primary immunodeficiencies, symptoms and signs can be detected at birth or during childhood.
Hemophilia is a congenital bleeding disorder in which the blood does not clot normally. It is caused by the deficiency of a certain protein – the clotting factor. People with hemophilia bleed easily and most often excessively. If left untreated, hemophilia can be life-threatening. Two forms are distinguished: Hemophilia A and Hemophilia B. Hemophilia A is the most common form, in which the activity of coagulation factor VIII is reduced; in hemophilia B, in turn, blood coagulation factor IX is not produced in sufficient quantities.
Approximately one in 10.000 newborns are born with hemophilia. It occurs primarily in male infants because it is a condition linked to the X chromosome. Worldwide there are an estimated 400.000 affected, with hemophilia A being far more common than hemophilia B, accounting for 80-85% of cases.
Hemophilia is suspected in patients with the following symptoms:
– Frequent bruising in early childhood. – Spontaneous hemorrhage (d.h. For no apparent/known reason), particularly in the joints, muscles, and soft ties. – Excessive bleeding after trauma or surgery.
Final diagnosis is made by a blood test to determine whether clotting factor VIII or IX is impaired.
Since hemophilia requires a different therapy depending on its manifestation, an accurate diagnosis is very important.
Hemophilia is treated extremely successfully by substitution of the impaired clotting factor. Therapy can be administered either "on demand," d.h. by treatment of an occurring hemorrhage, or "prophylactic" to maintain a clotting factor level with which bleeding is prevented. In developed countries, where these therapies are readily available, the life expectancy of men with hemophilia is essentially the same as that of the general male population. Both clotting factors can be isolated from donated human plasma. Also be produced using recombinant DNA technology. There are many commercial brands from which to choose, and this choice is generally made on the basis of availability, accessibility, price, and the risk of developing antibodies that would render the factor ineffective.
Srivastava A. et al. Guidelines for the management of Hemophilia. Haemophilia (2012), 1-47 Mannucci PM et al. How we choose factor VIII to treat hemophilia. Blood (2012) volume 119, number 18, 4108-4114
Von Willebrand syndrome
The most common bleeding disorder is von Willebrand syndrome (vWS), a congenital disorder caused by a deficiency or abnormality of a plasma protein essential for blood clotting, namely von Willebrand factor (named after the Finnish physician who first identified the disease).
Von Willebrand factor (vWF) is the "glue" that helps bind platelets in the blood to the vessel wall to form a plug where a blood vessel is broken. It also binds and stabilizes clotting factor VIII, so in patients with vWS, lack of vWF activity leads to premature elimination of factor VIII in the circulation, resulting in a double defect in the body's ability to stop bleeding. People with vWS produce normal amounts of factor VIII, but with deficient vWF, the clotting factor does not remain in the system long enough to perform its function adequately, as is the case in patients with type 1 and III vWS. Type I: The most common. Mildest form of the disease. In this form the vWF level is. Possibly also the factor VIII level is too low. – Type II: In this form of von Willebrand syndrome, there is normal and sufficient von Willebrand factor, but it is abnormal and does not function properly. The abnormality of the factor can vary, accordingly there are several subtypes of type II von Willebrand syndrome – it is important to determine this as treatment varies depending on the subtype. – Type III: The most severe form of vWS in which vWF is almost or completely absent and factor VIII levels are extremely low.
People with von Willebrand syndrome tend to bruise, have frequent nosebleeds that are difficult to stop, massively increased menstrual bleeding, and more severe and prolonged bleeding after injury, surgery, childbirth, or dental procedures. In its most severe form, vWS can lead to spontaneous joint and organ hemorrhage and can be life-threatening.
Some patients respond well to desmopressin acetate (DDAVP) injections, but the most effective treatment and prophylaxis for vWS, especially in its most severe forms, is therapy with plasma-based vWF products.
Federici AB. Classification and clinical aspects of von Willebrand disease. In: Textbook of Haemophilia 2nd Edition, Lee CA, Berntorp E, Hoots K (eds). Oxford: Wiley-Blackwell 2010. 302-308
Immune system disorders
In general, the immune system can be dysfunctional in three ways:
– Overactive or inappropriate immune response. – Lack of immune response. – Autoimmune response (defensive reaction against one's own body).
Asthma and allergies are examples of an overactive immune system reacting to a non-threatening foreign body.
Immunodeficiency and autoimmune diseases are mostly more severe and possibly life-altering diseases.
When one of the parts of the immune system is missing or not functioning well, we say that the immune system is defective. Usually involves absent or defective T or B lymphocytes or inadequate production of antibodies. The result is that the body is susceptible to infections that could otherwise be easily defeated.
Immunodeficiencies can be "primary" to be, d. h. Birth present. Usually genetic. Immunodeficiencies can be "secondary", secondary immunodeficiencies have many causes, including disease, malnutrition, aging, certain drugs, chemotherapy, radiotherapy and stress. Probably the best known, although not the most common, cause of immunodeficiency is human immunodeficiency virus (HIV), which can cause AIDS (acquired immunodeficiency syndrome).
There are approximately 185 primary immunodeficiencies recognized by the World Health Organization. Most common are those where antibodies are produced, these are called primary antibody deficiency (PAD). These disorders vary widely in their underlying defects, but many of them can be treated and their symptoms alleviated by regular administration of immunoglobulins.
Continued research and development of Kedrion has led to several immunoglobulin therapies for these diseases. Replacement therapy with immunoglobulin in PAD increases life expectancy and decreases infection incidence and severity.
Abbas K. et al. "Le basi dell'Immunologia. Fisiopatologia del sistema immunitario". Ed. Masson Elsevier 2006.
The human body can sometimes become its own worst enemy. For reasons that are still not fully understood, the human immune system sometimes loses its ability to distinguish between self and foreign and begins to attack normal healthy cells in the body. This disorder is called autoimmune disease.
There are numerous autoimmune diseases that affect millions of people and their incidence is on the rise worldwide.
Intravenous administration of immunoglobulin (IVIg) is indicated and approved for the following autoimmune diseases:
Immune thrombocytopenia (ITP). Immune thrombocytopenia, formerly also called idiopathic thrombocytopenic purpura, is an autoimmune bleeding disorder in which the immune system attacks its own platelets, which are important for the clotting process. For reasons that are not exactly clear, the lymphocytes produce antibodies that bind to these platelets and thus impair their clotting, which is why they are subsequently identified as "foreign" and destroyed in the spleen. Frequent and abnormal bleeding is typical and often results in many small hematomas that may look like a rash (purpura).
Navarro RP et al.Considerations for the Optimal Use of Immunoglobulin. Am J Manag Care. 2012;18:S67-S78. Abrahamson PE. The incidence of idiopathic thrombocytopenic purpura among adults: a population-based study and literature review. Eur J Haematol..2009 Aug;83(2):83-9.
Kawasaki syndrome. Also called mucocutaneous lymph node syndrome, is a form of vasculitis characterized by inflammation of blood vessels throughout the body. It mainly affects children under five years of age. Rarely children over eight years of age).
Properly treated, these children have a good prognosis, but without therapy, about a quarter develop heart problems. This is how aneurysms of the coronary arteries can develop. Kawasaki syndrome is the most common cause of acquired heart disease in childhood in industrialized countries.
Its origin is still unclear. Research is divided as to whether it is an infection or an autoimmune response. Intravenous administration of immunoglobulin is among the most effective treatment methods.
Uehara R, Belay ED. Epidemiology of Kawasaki disease in Asia, Europe, and the United States, J Epidemiol 2012; 22 (2): 79-85. Takahashi K et al.Pathogenesis of Kawasaki disease. Clinical and Experimental Immunology, 2011; 164 (Suppl. 1): 20-22. Newburger JW. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114:1708-1733.
This is a rare (1-2 cases per 100.000 population) autoimmune disorder in which the immune system attacks the myelin layer (outer layer) of peripheral nerves (and sometimes the nerves themselves). The damage causes tingling and weakness in the legs and can progress to life-threatening paralysis.
Generally, symptoms peak within days or weeks and remain stable in the subsequent plateau phase for days, weeks, or even months. Most people recover even from the most severe cases, but this recovery process can last from a few weeks to several years. The mechanisms of origin of this autoimmune response are not yet clear, but it is sometimes triggered by infection, surgery, or vaccination.
One therapy for Guillain-Barre syndrome that can reduce symptoms and speed recovery is high-dose administration of immunoglobulin.
Chronic inflammatory demyelinating polyneuropathy (CIDP)
CIDP can be considered a chronic form of Guillain-Barre syndrome caused by demyelination of peripheral nerves leading to numbness and motor and sensory deficits.
Its estimated prevalence is between 0.8 and 8.4 cases per 100.000 inhabitants. CIDP is a disease with frequent disability sequelae, with more than 50% of patients becoming temporarily disabled and about 10% becoming permanently disabled or dying from the disease sequelae.
The causes of CIDP remain unexplained, but there is evidence of immunopathogenesis. Plasmapheresis (plasma exchange), oral corticosteroids, and intravenous immunoglobulin (IVIg) are effective forms of treatment, but they should be started early to avoid permanent nerve damage.
Pithadia AB et al.; Guillain-Barre syndrome (GBS). Pharmacological Report 2010; 62: 220 – 232 Koller H et al.; Chronic inflammatory demyelinating polyneuropathy. N Engl J Med.2005 Mar 31;352(13):1343-56 Mahdi-Rogers M et al.; Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins. Biologics. 2010 Mar 24;4:45-9 E. Nobile Orazio. Intravenous immunoglobulin versus intravenous methylprednisolone for chronic inflammatory demyelinating polyradiculoneuropathy: a randomised controlled trial.