ANATOMY:
The spleen is located in the left hypochondrium in the diaphragmatic dome. The normal rate measuring 10 to 12 cm in height and it is not palpable.
In adulthood, the spleen has a role as defense barrier against encapsulated bacteria, physiological destruction of red blood cells.
The spleen is an organ with multiple functions:
– Hematopoietic (embryonic period);
– Lymphocytic;
– Erythrophagocytosis.
It participates in the primary immunity against particular encapsulated germs and parasites.
It has a temporary role in hematopoiesis during fetal life. However, this function may wake up during certain pathologies.
DIAGNOSIS:
Highlighting splenomegaly is relatively simple, different examination techniques have been described.
A large spleen is sometimes visible to the inspection, this especially in children.
Palpation is done with the patient supine strict, the examiner on the right. With the right hand flat, oriented top and side, we look for the lower pole of the spleen.
If the spleen is not palpable spontaneously, the patient is asked to inhale deeply.
Another technique for palpation is the patient supine right side, the raised arms, the physician stands behind the patient and search the lower pole of the spleen with hooked fingers.
The discovery of an enlarged spleen should be investigated lymphadenopathy, hepatomegaly, collateral circulation, ascites, jaundice, fever …
The geographical origin is important to note, as well as travel, recreation, alcohol intake and the existence of risk factors for HIV infection and chronic hepatitis.
IMAGING:
Ultrasound remains the most accessible examination, splenomegaly is defi ned by céphalocaudale distance greater than 13 cm. This examination will also study the splenic parenchyma looking for heterogeneity and allows vascular Doppler analysis in the case of a possible portal hypertension.
However, ultrasound is less than the scanner (with injection) for the splenic parenchyma of the analysis and research of bleeding or vascular lesions. It is important to know that the blood supply is often heterogeneous spleen causing a false appearance defect to the scanner. Before concluding a splenic lesion, it is necessary to analyze the different vascular time.
The magnetic resonance imaging study with vascular examination is a useful time to better characterize some lesions, it is by no means a first-line examination. The normal rate is a less intense signal in T1 and T2 more intense compared to those of the liver.
BIOLOGY:
It is important to clarify whether or not there is an inflammatory syndrome.
The blood count is fundamental to the search for quantitative abnormalities of various lineages, abnormal or activated cells.
Electrophoresis of serum proteins research an aspect of β-γ block, hyper- or hypogammaglobulinemia, monoclonal peak.
It seems that haptoglobin should be part of the initial assessment of splenomegaly, a low rate reflects generally hemolysis.
ETIOLOGY:
We will group them according to their mechanism:
– Infectious splenomegaly;
– Hemolysis with splenomegaly;
– Splenomegaly ystémiques s disease;
– Splenomegaly vascular;
– Tumor splenomegaly.
Infectious splenomegaly:
Bacterial splenomegaly:
Bacterial endocarditis:
It is primarily the subacute form or Osler disease that is accompanied by splenomegaly in almost 40% of cases.
Clinical features of fever, poor general condition, a heart murmur.
Sometimes it’s a feverish heart failure.
The skin symptoms were found in 15% of cases. Thus, a petechial purpura, the Osler’s nodes in the fingertips and toes (fleeting) and erythema Janeway.
The complications that are sometimes revealing primarily due to septic emboli: brain abscess or liver-spleen, meningitis, mycotic aneurysms, arthritis and spondylitis, arterial ischemia …
The diagnosis should be systematically suspected in prolonged fever, febrile heart murmur, febrile splenomegaly, fever in an addict or after certain actions.
Blood cultures are systematic and repeated, including echocardiography by trans-oesophageal way became the basis of diagnosis.
The spleen is the seat of simple hyperplasia, abscess or infarction.
The most commonly involved germs (excluding context of cardiac surgery) are streptococcus, staphylococcus aureus and enterococci.
Sometimes the diagnosis is made difficult by the negative nature of blood cultures or following previous use of antibiotics, or in the case of genuine endocarditis with negative blood cultures.
In the latter case, the causative organisms are deficient streptococci, Chlamydia, Coxiella burnetii (Q fever agent), and Legionella bacteria HACEK group.
The group brings together HACEK Haemophilus genres, Actinobacillus, Cardiobacterium, Eikenella and Kingella.We tend to add to the kind Capnocytophaga (HACCEK group). Their common point is that they are gram-negative bacilli very slow growing.
A special mention for Kingella whose peculiarity is the occurrence of rapidly destructive valvular lesions and high mortality.
Treatment is based on parenteral antibiotics in hospitals, rapidly bactericidal and high dose. Close monitoring is necessary to detect and prevent very common complications.
Brucellosis:
This is an infection with a gram-negative bacillus of the genus Brucella. It is a zoonosis that primarily affects ruminants. Contamination is professional (farmers, butchers …) or food (milk or unpasteurized cheese).
It may also be an imported pathology (about 2760 cases in Algeria and 14,400 in Turkey in 2003). The spread of the germ is lymphatic. The incubation period is 1 to 2 weeks.
It carries the table sudoro-Algonkian fever (undulant fever, arthralgia, headache, myalgia and abundant night sweats) in septicemic phase. Splenomegaly is common at this stage (1/3 of cases).
The standard biology shows off the inflammatory syndrome, leucopenia, lymphocytosis and moderate hepatitis.
Diagnosis is based on blood cultures in the primary phase and serology.
Achieving splenic also met the secondary and late phases usually in the form of “brucellome” that are the equivalent of cold abscesses. It is exceptional in France and is rather encountered in patients from countries with low health means.
Antibiotic treatment should involve a tetracycline (doxycycline) and rifampicin (Rifadine®) for 30 to 45 days, or tetracycline and aminoglycosides. In children and pregnant women, tetracycline can be replaced with cotrimoxazole.
Q fever:
It is an infection caused by Coxiella burnetii, strict intracellular bacterium. Contamination is mainly aerial livestock contact, placenta of newborn animals and contaminated wool. The other mode of contamination by digestive eating contaminated raw milk products. More rarely, some pets when they give birth, can be contaminants for humans. In France, the disease is most common in the Southeast, it remains underdiagnosed.
In the acute phase, it carries a feverish table with isolated or associated with fever disease (interstitial most often) and / or biological hepatitis. Splenomegaly is found in approximately 30% of patients.
Biology showed inflammatory syndrome, cytolysis, often the absence of leukocytosis, thrombocytopenia sometimes.
The chronic form is ie lasting for more than 6 months, is characterized by cardiovascular disease (endocarditis in 70% of cases, aneurysms infections). Splenomegaly and hepatomegaly are mostly encountered in endocarditis.They can rarely be large. However chronic Q fever is rare (5%).
Diagnosis is based on serology seeking the phase I and II antibodies. In acute forms are phase II antibodies that are raised, Song IgM> 1/50 IgG> 1/200 is specific for acute infection. In chronic forms there is a rise of antibodies phases I to much higher and still higher phase II antibody levels. Thus, a titre> 1/800 antibody Phase I is sufficient to confirm endocarditis.
The active antibiotics are tetracyclines (doxycycline 200 mg / day), rifampin (600 mg / d), quinolones and macrolides.In the acute form, the antibiotic of choice is doxycycline (100 mg / 2x / d) Recommended for 3 weeks, but probably enough raient two weeks.
In endocarditis, prolonged treatment is necessary, a minimum of 18 months by the association doxycycline 200 mg / day and hydroxychloroquine (Plaquenil®) 600 mg / d or 3 cp / day.
The dosage of hydroxychloroquine is to adapt to serum.
A relative is the bacterial genus Rickettsia.
Splenomegaly was found in 40% of cases of fever of the Rocky Mountains. It is also observed in African rickettsial (back safaris). It is much rarer in the Mediterranean spotted fever.
Typhoid fever:
It is due to major salmonella typhi and Salmonella Paratyphi. This is an import pathology more often the door is digestive (water and food) and lymphatic spread is. The incubation period is 7-15 days, the onset may be gradual or abrupt.
Digestive disorders, fever between 39 and 40 ° C, a pulse-temperature dissociation are evocative. Splenomegaly is found in the first week but especially during the second week.
Diagnosis relies on the detection of the organism in blood cultures (positive during the first week) in stool cultures (to be repeated).
Serology is positive that from the eighth day he must beware of false positives (Yersinia, Candida). A leukoneutropenia or absence of leukocytosis is classic.
Treatment should involve effective antibiotic therapy and symptomatic measures. The most consistently effective antibiotics are the third generation cephalosporins and fluoroquinolones.
Quinolones have the advantage with oral ofloxacin (Oflocet® 200 mg / 2x / d) or ciprofloxacin (500 mg Ciflox® / 2x / day) for 5 days.
Cephalosporins are used preferentially in children: ceftriaxone (Rocéphine®) 75 mg / kg / day or a maximum dose of 4 g / day for 5 days.
Yersiniosis:
They are caused by Yersinia pseudotuberculosis and Yersinia enterocolitica. Contamination is digestive.
Several clinical forms are possible, mostly benign. However septicaemic forms may be responsible for suppurative hepatic localizations, spleen or bone and joint. These severe forms occur preferentially in certain fields (elderly, AIDS, cirrhosis, hemochromatosis, thalassemia, sickle cell anemia).
Another feature of these germs is the occurrence of reaction events (erythema nodosum, reactive arthritis, cutaneous vasculitis …).
Splenomegaly was found in case of suppurative lymphadenitis mesenteric or splenic localization.
Diagnosis can be made by blood cultures, stool cultures or serology (examination to be interpreted with caution since false positives are many).
Effective antibiotics are systemic quinolones, third generation cephalosporins, tetracyclines, macrolides.
Tuberculosis:
Splenomegaly is seen in miliary forms (hematogenous spread). It is associated with severe impairment of general condition, often high fever, hepatomegaly or meningeal signs.
We must seek tubers Bouchut at the fundus.
Biology shows cytopenia may carry on 3 lines, rarely leukocytosis, elevated alkaline phosphatase.
The anergy is classic.
The cultured must be multiple and repeated (sputum, Tubing, urine, bone marrow …), direct examination is rarely positive.
Treatment should be initiated quickly based on clinical and radiological presumption arguments (miliary one or more organs).
It should detect underlying immunosuppression, indeed extra-pulamonaires disseminated forms are more common in im munodéprimés (AIDS, corticosteroids, dialysis, transplant …).
The treatment is that of the classical tuberculosis.
Leptospirosis:
It is caused by bacteria of the genus Leptospira. Human contamination occurs accidentally due to a bite or contact with contaminated water (farmers, sewer workers, farmers and recreational freshwater). Rodents (rats) are the main reservoir.
The clinical picture is noisy with high fever, aches and diffuse mucocutaneous manifestations.
The liver injury is the most frequent visceral involvement. Splenomegaly is possible septicemic stage although rarely in the foreground.
The treatment is explained in Chapter hepatomegaly .
Recurrent fevers:
This is of import pathologies caused by borreliosis. We distinguish:
– The cosmopolitan relapsing fever Borrelia recurrentis, transmitted by lice and that affects the displaced population;Tick-borne relapsing fever affecting some rural areas in the world.
The clinical picture is characterized by a significant sudden fever with chills and diffuse pains.
Splenomegaly is common in the initial phase and is in a free general.
The natural course is characterized by recurring periods of calm and febrile phases become shorter.
The diagnosis is primarily clinical, there is a neutrophilic leukocytosis, an inflammatory syndrome, anemia and cytolysis.
For antibiotics there is a choice between beta-lactams, macrolides and tetracyclines. The recommended time is 5 to 10 days.
Splenic abscess:
Rather, it is a picture of the feverish pain with left upper quadrant frequent leukocytosis, splenomegaly is found regularly but is not constant. The causative organisms are primarily gram-negative bacilli and gram positive cocci, we must also think of salmonellosis, brucellosis. In immunocompromised should also be mentioned as yeast candida. Some parasites may be involved.
Treatment is a broad spectrum antibiotic parenterally, the initial focus of control (endocarditis, colonic lesion …).Splenectomy or percutaneous drainage may sometimes be necessary.
Viral splenomegaly:
Infectious mononucleosis:
It is caused by the Epstein-Barr virus (EBV).
The classic table combines a deep fatigue, mild fever, bilateral erythematous pultaceous angina, purpura soft palate, eyelid edema and uvula, generalized lymphadenopathy sometimes but usually predominant on the upper trunk, a measles-like rash of the trunk and the root of the members especially if there has been taken ampicillin.
Splenomegaly is frequent (50% of cases), it is soft and painless. We must be careful because there is a rare risk of spontaneous splenic rupture. Other complications are possible: peripheral thrombocytopenia, autoimmune hemolytic anemia, polyneuropathy, cérébellite, hepatitis …
Standard biology shows (apart from complications) mononucleosis which in fact corresponds to the presence of activated lymphocytes hyperbasophilic, cytolysis and a moderate thrombocytopenia.
Definitive diagnosis relies on serology in immunocompetent:
– MNI-test rapid realization, but it is negative in 10-30% of cases, especially in children;
– Specific serology signing primary infection when she highlights VCA IgM.
Research and quantification of the viral genome have no interest in conventional acute forms, they are useful against in immunocompromised or to atypical tables or suspected viral reactivation.
Note that EBV can cause lymphoproliferative splenomegaly may give the tumor.
There is no specific treatment for infectious mononucleosis except for the symptomatic treatment and the complications. Antiviral active on some Herpesviridae never proved a real clinical efficacy in case of EBV infection.
Cytomegalovirus:
Infection by cytomegalovirus (CMV) often goes undetected in children, it is more commonly symptomatic in adults plateau fever with or without chills, fatigue, arthralgia, headache, pharyngitis.
On physical examination, splenomegaly is present in 25% of patients, also hepatomegaly and superficial lymphadenopathy.
Mononucleosis appears towards the tenth day often associated with moderate cytolysis.
This mononucleosis is less intense than with EBV.
Diagnosis is primarily based on serology with the demonstration of specific IgM but not IgM antibodies can differentiate a primary infection from reinfection can last several months and may lack in immunocompromised patients. It is optionally possible to demonstrate seroconversion of IgG two weeks apart. Otherwise you can search viremia rapid culture (24-48 hours) or viral antigenemia (6 hours delay). Viremia and antigenemia remain positive for 2 to 3 weeks. Both techniques are also possible on other body fluids but with less sensitivity.
The search for the viral genome by polymerase chain reaction (PCR) has no real utility in classical infection.
Treatment of CMV infection is necessary in immunocompromised patients with complications or severe visceral involvement (chorioretinitis, gastrointestinal involvement, central nervous system). In immunocompetent, treatment can be discussed in severe cases of infection especially if there is a potentially serious organ involvement, in any case there is no consensus about it.
Effective molecules are ganciclovir (Cymevan®), foscarnet (Foscavir®) and cidofovir (Vistide®). Ganciclovir is available in oral and injectable forms, it is used at a dose of 5 mg / kg / 12 hours for 14 to 21 days and then switched to oral depending on the circumstances. The other two molecules are available only in injectable. All these molecules have an average tolerance profile. Valaciclovir (Zelitrex®) is not indicated in the curative treatment currently indicated as a preventive after organ transplant.
HIV:
The HIV primary infection may be responsible for splenomegaly. This is a reaction sometimes accompanied by splenomegaly mononucleosis.
In a patient who developed AIDS, the appearance of an enlarged spleen should be investigated as a complication hematogenous tuberculosis, atypical mycobacterial infection or lymphoma.
Parasitic splenomegaly:
Malaria:
Splenomegaly may be during severe illness. It is reversible after effective treatment. Treatment should be tailored to the zone contagion and clinical manifestations.
In the absence of severity of signs and digestive disorders, treatment can be done at home:
– Chloroquine area: Nivaquine® 5CP / d for 5 days and then 1 tablet / d;
– Chloroquine-zone: oral quinine at a dose of 8 mg / kg / 8h basic quinine for 7 days.
If signs of severity or digestive problems making random oral intake, treatment
hospital to be preferred.
Chronic and massive splenomegaly occurs during the evolutionary visceral malaria, it is also the main clinical manifestation.
This situation occurs after repeated infections in low immunized subjects especially children in malaria-endemic countries but also expatriates adults moderately infested with chloroquine-sensitive strains.
Clinical features asthenia, massive splenomegaly with périsplénite, a low-grade fever and anemia. There is no examination to the formal diagnosis, malaria serology is always positive. We consider that an answer to pest control is a major diagnostic criterion; must splenomegaly decreases of over 40% in 6 months.
Leishmaniasis:
It’s visceral leishmaniasis due to Leishmania donovani (India and East Africa) or Leishmania (Central Asia, Mediterranean, Central America and South America). The visceral form that can be encountered in France is called Kala-Azar, there are two main centers (Corsica Mediterranean South).
Transmission to humans by bite of the sandfly.
The table combines a typically anarchic fever, a major splenomegaly, firm, painless and mobile. There may be small lymph nodes and sometimes hepatomegaly.
It joins in an inflammatory syndrome, predominant on IgG hypergammaglobulinemia, pancytopenia.
The diagnosis is aided by serology which has a sensitivity of 95%. The formal proof is provided by the direct detection of Leishmania in bone marrow aspiration.
Treatment in Europe currently relies on liposomal amphotericin B: AmBisome 3 mg / kg weekly injection for 5 days with a booster shot on the tenth day. A molecule that has proven effective in the Indian form, miltefosine (old product chemotherapy) at a dose of 2.5 mg / kg / day orally for 28 days.
Schistosomiasis:
It is caused by Schistosoma mansoni and Asian schistosomiasis (Schistosoma japonicum and Schistosoma mekongi which is very close).
S. mansoni is present in the Caribbean, Latin America (tropics), the Middle East and Africa (excluding the Maghreb).Asian schistosomiasis are distributed in Japan, China and Southeast Asia.
Splenomegaly appears from the acute phase with infiltration of eosinophils and miliary granuloma formation.Secondarily, splenomegaly will grow especially due to portal hypertension with splenomegaly sometimes monstrous. Blood eosinophilia is common.
Diagnosis is helped by research schistosome eggs in stool, knowing that their excretion is intermittent. Rectal biopsy seems the most sensitive technique. Serology by indirect immunofluorescence or ELISA (Enzyme-linked immunosorbent assay).
Treatment is praziquantel (Biltricide®) that is active on all species and well tolerated.
The dosage is 40 mg / kg once daily for Schistosoma mansoni. Against by a different pattern is used to japonicum mekongi 3 taken 20 mg / kg given every 4 hours each. A second cure is possible for those who keep positive stool.
Another molecule is available oxamniquine (Vansil®) but its use is limited because only active on Schistosoma mansoni.
Other:
Splenomegaly may be found in amebiasis, toxoplasmosis, hydatid disease and very rarely during histoplasmosis.
The splenic radiation reaching discovery being more common (abscess).
Hemolysis with splenomegaly:
Chronic hemolysis is accompanied by splenomegaly.
Membrane congenital hemolytic anemia:
This is the case of hereditary spherocytosis, hereditary elliptocytosis, hereditary and ovalocytosis stomatocytoses.
Anemias hemoglobinopathies:
These are α and β thalassemia, mainly intermediate and major forms.
The sickle cell disease is a special case.
Indeed, splenomegaly is found in the first years of life. Subsequently, the spleen is the seat of myocardial spleen responsible for some atrophy and loss of function.
Anemia by hemolysis extracorpusculaire:
Myelofibrosis is rare. They can be mechanical (valve replacement or vascular thrombotic microangiopathy).
They can be infectious as in malaria attacks, Carrion’s disease.
Autoimmune hemolytic anemia:
Splenomegaly was found in 50% of chronic forms. Acute hemolysis is accompanied rarely splenomegaly.
Biology shows anemia (which may miss if hemolysis is compensated), reticulocytosis, a collapsed haptoglobin, LDH and high indirect bilirubin. The direct Coombs test is positive.
The treatment is based primarily on corticosteroids, immunosuppressants second line.
Splenectomy should be avoided if possible.
Paroxysmal nocturnal hemoglobinuria:
It is a clonal disease of the hematopoietic stem cell responsible for chronic hemolysis with possible acute attacks.
Diagnosis is currently lodged with polymorphic clinical pictures.
A chronic hemolysis table not acquired autoimmune must do this disorder.
Are then found mild jaundice, moderate splenomegaly and anemia.
The classic morning hemoglobinuria (hence the name of the disease) is not always present, it may even be permanent.
Evolutionary risks are atypical venous thrombosis, increased risk of infection and usually late myelosuppression.These events are sometimes indicative of the disease.
Diagnosis is by flow cytometry which confirms the presence of a red cell clone and / or leukocyte CD55- and CD59- (PNH).
Treatment is difficult: immunosuppressants, transfusion support, bone marrow transplantation (only potentially curative treatment).
A new treatment using a monoclonal antibody against C5 complement fraction, eculizumab, is in clinical evaluation.
The results are encouraging in terms of reduction in transfusion requirements.
By enzyme deficiency anemia:
These deficits G6-PD (glucose dehydrogenase-6-phosphate) or favisme and pyruvate kinase deficiency.
G6PD deficiency is responsible for a hemolytic anemia triggered by infections, certain medications or when ingesting beans. This deficit is especially prevalent in populations of black Africa and mé ranean basin.Transmission is X-linked recessive (homozygous hemizygous boys and girls) with a variable phenotype. The diagnosis is made by measurement of the enzymatic activity outside of hemolytic crisis.
Pyruvate kinase deficiency is autosomal recessive responsible for chronic haemolysis of varying intensity. The first diagnostic step is the determination of erythrocyte enzyme activity.
Splenomegaly and systemic diseases:
Systemic lupus erythematosus:
Splenomegaly is found in up to 20% of patients, usually during a push. It is rarely symptomatic, persistence must fear lymphoma or an infectious complication in these immunocompromised patients.
Another element is found sometimes the existence of a functional hyposplenism.
Felty’s syndrome:
This particular feature is described in rheumatoid arthritis and associated by definition splenomegaly and neutropenia. Currently we tend to designate in excess, to as Felty syndrome, neutropenia
isolated during rheumatoid arthritis.
Location uncommon (<1%), which sees itself in rheumatoid arthritis old and scalable. Treatment is difficult and based on corticosteroids, immunosuppressants (methotrexate, leflunomide [Arava®]). The anti-TNF seem ineffective this complication.
The hematopoietic growth factors (G-CSF: Granocyte®, Neupogen®) are to be reserved for deep neutropenia and / or infection episodes, their prolonged use should be carefully weighed.
It may be compared to lymphocytosis large granular lymphocytes (LGL cells) which can also complicate rheumatoid arthritis. This gives splenomegaly, neutropenia, lymphocytosis and thrombocytopenia.
It is a clonal lymphocyte proliferation phenotype CD3 +, CD8 +, CD57 +. The treatment is also that of rheumatoid arthritis (methotrexate), optionally cyclosporin A.
Macrophage Activation Syndrome:
This is a clinicopathological syndrome that combines clinical, biological and hemophagocytosis.
Clinical features impaired general condition, fever and frequent organomegaly.
As splenomegaly is present in 30-60% of cases, usually associated with hepatomegaly and sometimes lymph nodes.
Biology is evocative to an inflammatory syndrome, pancytopenia (sometimes limited to 1 or 2 lines at the beginning), elevated LDH and triglycerides and often major ferritin. The demonstration of haemophagocytosis (phagocytosis of blood elements) is required for diagnosis.
It may be present in the bone marrow, liver, lymph nodes, spleen.
However to retain the diagnosis requires histology is associated with a compatible clinical picture.
Indeed, there is a minimal haemophagocytosis to the physiological condition,
The causes of this syndrome are infectious and foremost viral (EBV especially), systemic diseases (lupus, Still’s disease), lymphomas (rarely solid tumors) and immunodeficiencies.
Treatment should be symptomatic (correction cytopenias when there is a vital risk), etiologic. Depending on circumstances, it may be necessary to act on the process hemophagocytosis (steroids, etoposide, immunoglobulins).
Immunodeficiencies:
Splenomegaly is sometimes develops in immune deficiencies including deficiencies of humoral immunity. The spleen is the site of hyperplasia. However, it should always be wary of a possible complication infectious (tuberculosis …) or tumor (lymphoma …).
The most often discovered immune deficiency in adults is common variable immunodeficiency or CVID. Diagnosis is usually in front of ENT infections, pulmonary or digestive repeated.
To retain a CVID, there must be a hypogammaglobulinemia with a deficit at least as to two classes or two subclasses of immunoglobulins.
The treatment is useful in symptomatic patients, intravenous infusions of polyvalent human immunoglobulin (0.3 to 0.5 g / kg every 4 weeks) or subcutaneously (at home).
Sarcoidosis:
Splenomegaly occurs in 10% of systemic sarcoidosis sometimes with a pseudo-nodular form.
Apart splenomegaly rarely seen in thyrotoxicosis and whose mechanism is obscure, histology corresponds to a benign lymphoid hyperplasia.
Vascular splenomegaly:
It is primarily the spleen by portal hypertension found in cirrhosis (regardless of origin) at a door obstruction (thrombosis, tumor compression) at the hepatic vein thrombosis (Budd-Chiari syndrome and disease veno-occlusive liver), liver schistosomiasis (with or without cirrhosis) and echinococcosis.
Much more rarely splenomegaly may result from the splenic vein thrombosis or aneurysm of the splenic artery.
Splenomegaly infiltration:
No tumor infiltration:
Ectopic Myelopoiesis:
The spleen may be the site of ectopic myelopoiesis in various situations such as idiopathic myelofibrosis, invasion of bone marrow by malignant cells (solid tumors or acute leukemia) or benign as in Gaucher disease.
Splenomegaly is usually firm and can reach considerable proportions.
Gaucher disease:
It is due to a defi cit in â-glucocerebrosidase leading to the accumulation of glucosylceramide.
The gene is located on chromosome 1q21.
It recognizes three types based on clinical manifestations. Splenomegaly is found in type I, which is also the most common.
Other manifestations are bone (osteonecrosis, deformities and pain) and hepatomegaly.
Splenomegaly was due to a splenic infiltration by Gaucher cells but may be the result of an ectopic myelopoiesis.
The diagnosis is suggested by the presence of Gaucher cells in the bone marrow aspirate (non-specific), the measurement of the enzymatic activity of β-glucocerebrosidase and the search for the mutation by PCR (for the five most common mutations).
Treatment is based on the substitution with imiglucerase (Cerezyme). A new treatment is currently available, miglustat (Zavesca®), it is less effective than replacement therapy. The terms are detailed in the “Hepatomegaly”.
Niemann-Pick disease:
This is the type B which is manifested initially by hepatomegaly and splenomegaly, there are no neurological signs but appears belatedly lung damage type alveolar infiltration.
Tangier disease:
This is an exceptional disease responsible for a severe deficiency in HDL-cholesterol.
It is manifested by large tonsils with yellow tonsils, splenomegaly and hepatomegaly, neuropathy and coronary disease (risk multiplied by six beyond 30 years).
The bodies are the site of deposits of cholesterol esters.
Biology finds a free fall or even the absence of HDL-cholesterol and apolipoprotein A1. It often has a moderate decrease in LDL and hypertriglyceridemia.
Amyloidosis:
It is especially AL amyloidosis that can give splenomegaly, about 10% of patients.
The hyposplenism is significantly more common (25% of amyloidosis). Cytology often found thereby Jolly bodies, rarely cytopenia.
Mucopolysaccharidoses:
This is a group of diseases that share a deficiency of a lysosomal enzyme involved in the degradation of glycosaminoglycans whose accumulation is responsible for the disease.
The classification was initially based on clinical and biological phenotype, it has been modified since the determination of genes and enzyme deficiencies involved to bring some forms initially separated.
Roughly, they share a skeletal and joint damage, heart damage and a more or less severe CNS type of mental retardation (absent in some forms).
Those accompanied regularly splenomegaly (enlarged liver often associated with them) are the type IH (Hurler syndrome), type IH / S (Hurler-Scheie syndrome), type II (Hunter syndrome) type VII (Sly syndrome). It is sometimes found in the type III (Sanfi lippo syndrome).
Most often the diagnosis is made in childhood but attenuated forms recognized in adolescence or in young adults exist for Hurler-Scheie, Hunter and Sly.
Tumor infiltration:
Systemic mastocytosis:
These are conditions characterized by the accumulation of mast cells in tissues. We speak of systemic mastocytosis when the infiltration is not limited to the skin.
Splenomegaly is seen in 40-60% of systemic mastocytosis, it is usually associated with hepatomegaly.
Other manifestations are paroxysmal flushing, headache, a very common skin disease (urticaria pigmentosa, telangiectasia), bone involvement (sclerotic lesions, lytic lesions identified by a condensed border, osteoporosis), gastrointestinal disease (frequent abdominal pain, diarrhea , malabsorption).
Biology found an elevation of histamine and the serum tryptase.
The diagnosis is before a formal compliant histology (bone marrow, liver, skin …).
Treatment is often difficult: eviction foods and substances which may degranulate mast cells, anti-H1 antihistamines and H2 blockers. The anti-H1 is most effective on the flush and pruritus, especially useful H2 for digestive symptoms.
Corticosteroid therapy has often that suspensive effect and to be reserved for severe cases.It can be used in local treatment such as budesonide (Entocort®) per os , a molecule with low systemic bioavailability, potentially effective on severe digestive disorders.
Imatinib (Gleevec) is effective only in the forms not having the c-kit mutation. It was suggested that interferon α or cladribine, with mixed results.
Waldenstrom’s disease:
It is currently one of lymphoproliferations marginal zone.
It combines a monoclonal IgM and clonal proliferation lymphoplasmacytic (bone marrow aspiration and bone marrow biopsy). Splenomegaly is found in half the cases. Other possible symptoms include peripheral neuropathy, gastrointestinal involvement (tumor infiltration of the digestive tract), cutaneous vasculitis and hyperviscosity syndrome (for IgM> 30 g / L).
The treatment is not systematic, often a simple monitoring is required at the beginning.
When treatment is necessary, the molecules that can be used: chlorambucil, cyclophosphamide, fludarabine, α-interferon.
In severe forms combination chemotherapy is needed.
Hodgkin’s disease:
It is a lymphoid hematological B characterized by the presence of Reed-Sternberg cells.
The usual form affects young adults or adolescents and with neck and / or mediastinal lymphadenopathy. The presence of splenomegaly in such cases worsens the disease staging by passing in stage III (above and below the diaphragm). Indeed spleen is considered a node group.
The treatment is based on chemotherapy followed by radiation therapy to the lymph nodes in localized forms.
Chronic myeloid leukemia:
Most often, the picture is insidious, splenomegaly was found in 50% of cases.
There may be an alteration of the general state.
Biology shows a predominant leukocytosis on polynuclear but also other lines, frequent myelemia.
The diagnosis is confirmed by molecular biology highlights the Bcr-Abl transcript.
Treatment was revolutionized by the arrival of tyrosine kinase inhibitors, the first on the market was imatinib mesylate (Glivec). Others are currently available.
It is the only drug therapy capable of inducing cytogenetic and molecular response in contrast to older treatments (Hydrea®, interferon α).
Allogeneic bone marrow remains in theory the only treatment curator until we have sufficient perspective on treatment with imatinib.
Other myeloproliferative disorders:
These are polycythemia vera (red line), essential thrombocythemia (platelets) and idiopathic myelofibrosis. They are often accompanied by an enlarged spleen, which can be painful.
These three diseases are currently being modified diagnostic criteria after the detection of cytogenetic and molecular abnormalities. Thus translocation called Jak-2 is found in blood cells of patients with polycythemia (> 95% of patients) and in almost 50% of patients with idiopathic thrombocythemia or myelofibrosis and have a more severe clinical picture.
For now this anomaly does not impact in terms of treatment. The molecules are available pipobroman (Vercyte®) and hydroxyurea (Hydrea®).
Hairy Cell Leukemia:
It is accompanied by a frequent splenomegaly (75%). Usually there are no devices or deep lymph nodes. There is a male and a preferential reached after 50 years and among farmers (in France). Another mode of revelation is that of an opportunistic infection or tuberculosis.
The blood count is suggestive when there is classical pancytopenia. The hairy are constantly present in the blood smear analyzed by an experienced cytologist. This is confirmed by flow cytometry (lymphocyte immunophenotyping).
The spleen is the site of tumor infiltration.
Possible treatments include interferon α and purine analogs such as cladribine and Deoxycoformycin.
The α-interferon is used in courses of 12 months, but with a high rate of relapse a few months after stopping treatment. Splenectomy is a historical treatment.
Cladribine or 2-CdA (Leustatine®) has the advantage of a single course of treatment in 7 days (0.1 mg / kg / day), deoxycoformycin (Nipent®) is made of injection at a dose of 4 mg / m2 every 15 days. These two molecules cause a deep and prolonged neutropenia and immunosuppression with lower CD4 lymphocytes. Severe infectious complications are common.
The anti-CD20 monoclonal antibody (rituximab: Mabthera®) looks promising.
Splenic lymphoma with villous lymphocytes:
Splenomegaly may be large.
Usually there is no lymphadenopathy or hepatomegaly.
The presence of villous lymphocytes on blood smear is evocative and will be confirmed by immunophenotyping.
This is a low grade Disease.
Treatment is primarily splenectomy can be curative. If chemotherapy is needed, the molecule of choice is fludarabine.
Low-grade hematological:
We group in this context several entities whose prognosis, the cellular origin and the different treatment often.
This is the case of follicular lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia. This is also the case for the majority of splenic lymphomas.
Splenomegaly is searching and she was found in 40% of chronic lymphocytic leukemia.
High-grade B-cell lymphomas:
It includes search lymphomas rapid tumor kinetics: Anaplastic large cell lymphoma, Burkitt’s lymphoma …
Splenomegaly is possible but it is the background, the clinical picture combines superficial and / or deep lymph nodes, fever and impaired general condition.
Treatment consists of intensive chemotherapy and fast.
Lymphoma T:
It is a heterogeneous group of blood diseases. The type most commonly associated with splenomegaly is angioimmunoblastic lymphoma. There is also HSTCL (lymphoma γ / δ cells).
Anyway, splenomegaly is significantly more common in systemic T-cell lymphomas compared to B-cell lymphomas
Splenomegaly is rare in cutaneous T-cell lymphomas.
Malignancies spleen:
Apart lymphomas, it is mainly sarcomas. Diagnosis is difficult and often aided by imaging.
The management should be done in specialized centers.
Splenic metastases:
They are rare, splenomegaly is hard. We must seek melanoma, breast cancer or ovarian cancer first, other primitive are described (lung, cervix, colon …).
Usually this is at a very late stage of the cancer disease.
Benign:
They are rarely responsible for splenomegaly.
Include hemangioma, hamartoma, cysts.
CONCLUSION:
When splenomegaly accompanied by superficial lymph nodes, there is a very high probability that the case is unique.
The exploration of superficial nodes (puncture biopsy) greatly facilitates the diagnosis.
The clinically isolated splenomegaly problem is often very difficult.
Myelofibrosis has only incidental interest for the diagnosis when there is one obvious causes (sepsis, large viral infection, parasites, cirrhosis).
The blood count and reticulocyte account often brings decisive guidance.
When the clinical context and do not direct blood count, exploration becomes more difficult and in general is a specialized service: Liver exploration including the causes of portal hypertension;
– Ultrasound and / or scan in search of heterogeneity splenic (nodules) and / or deep lymph nodes whose presence makes it very likely the diagnosis of lymphoma and must lead to a profound lymph node biopsy or diagnostic splenectomy (to achieve if splenomegaly was heterogeneous, isolated and without bone marrow involvement);
– Marrow biopsy and bone marrow aspiration to search lymphoid hematological malignancy largely because myeloid malignancies will usually result in abnormalities of the blood count;
– Sometimes a diagnostic splenectomy is necessary particularly in large and scalable splenomegaly that are not proven.
Sometimes despite broad assessment, the nature of splenomegaly remains doubtful. In these cases it may be necessary to leave in place a moderate splenomegaly. It should however be certain of the possibility of regular monitoring (clinical, imaging and blood count), fear being in these cases splenic lymphoma.
