Primary tumors of the heart are rare; infact most are metastic tumors and almost 5% of people dying of malignancies have a metastasis in the heart. Although rare, primary cardiac tumors in decreasing order of frequency are as follows:
a) Myxoma
b) Fibroma
c) Lipoma
d) Papillary fibroelastoma
e) Rhabdomyoma
f) Angiosarcoma and other sarcomas
a) MYXOMA
These are the most common primary tumor of the heart in adults. Although they may arise in any of the heart chambers, 90% are located in the left atrium. Morphologically, the tumors are almost always single but rarely several may occur simultaneously. They range from small (<1cm) to large (upto 10cm). They are sessile, pedunculated masses that vary from globular hard masses mottled with hemorrhage to soft, translucent, papillary or villous lesions having a gelatinous appearance. The pedunculated form is frequently sufficiently mobile to obstruct the AV valves during systole. This movement can sometimes cause damage to the valves. They are composed of stellate or globular myxoma (lepidic) cells, endothelial cells, smooth muscle cells, and undifferentiated cells embedded within an abundant acid mucopolysacchiride ground substance and covered on the surface by endothelium. Hemorrhage and mononuclear infiltrates are also present.
Clinical manifestations are due to the valvular "ball valve" obstruction, embolization or syndrome of constitutional symptoms. Sometimes embolization brings attention to these lesions. Surgical removal proves to be curative, but rarely these neoplasms can occur again. Approximately 10% of patients have a familial syndrome (Carney's syndrome) which is characterized by cardiac and extracardiac myxomas, spotty pigmentation and endocrine overactivity.
b) LIPOMA
These may occur in the subendocardium or subepicardium or even within the myocardium, as localized, poorly encapsulated masses, which may be asymptomatic or cause ball valve obstruction as in myxomas. Some may even lead to arrythmias. They are mostly located in the left ventricle, right atrium or the atrial septum. Some may not even be neoplasms and simply be faty deposition called 'Lipomatous hypertrophy'.
c) PAPILLARY FIBROELASTOMA
These are curious, usually identical, lesions, most often identified at autopsy. They may give rise to embolize which might bring attention to them. Morphologically, they are usually located on the valves, particularly ventricular surfaces of semilunar valves and atrial suface of the AV valves. Histologically, they are covered with endothelium contained in myxoid connective tissue containing abundant mucopolysacchiride matrix and elastic fibers.
d) RHABDOMYOMA
They are the most frequent primary tumor of the heart in infants and children. And they are usually discovered in the first year of life due to obstruction of valvular orifice or cardiac chamber. Morphologically, they are generally small, gray-white myocardial masses upto several centimeters in diameter located in either of the heart sides protruding into the ventricles. Histologically, they are composed of mixed type of cells. The most characteristic cells are large, rounded or polygonal cells, containing numerous glycogen-laden vacuoles separated by strands of cytoplasm running from the plasma membraneto the nucleus (spider cells).
e) SARCOMA
Cardiac angiosarcomas are no different from such tumors in other areas of the body and thus will be dealt with in a separate article on Angiosarcomas. Other sarcomas will be covered in a separate article as well.
Most impacts of neoplasms on the cardiac anatomy are due to other factors. These are as follows:
a) Pericardial and myocardial metastases
b) Large vessel obstruction
c) Pulmonary tumor emboli
d) Nonbacterial thrombotic endocarditis (NBTE)
e) Carcinoid heart disease
f) Pheochromocytoma associated hypertensive disease
g) Myeloma related amyloidosis
h) Effects of chemotherapy and radiation therapy
Tuesday, January 27, 2009
Monday, January 26, 2009
Psoriasis
Psoriasis is a dermatological disease which is multifactorial in origin and characterized by formation of salmon pink colored plaques covered with silvery white scales present on bony prominences, extensor surfaces of the body and scalp. The scales have a typical shine to them.
Causative agents:
1) Genetic influence - positive family history; there are no specific genetic markers for the disease although it is more common for two monozygotic twins both to have the disease.
2) Autoimmune - lots of autoimmune disorders associated with the condition with a number of autoantibodies found in the serum of such patients.
3) Drug-induced - quite commonly used drugs are implicated in the condition such as antimalarials, B-adrenergic blockers, lithium and NSAIDs.
Idiopathic cause is also implicated. The condition is not curable and treatment involves palliative measures only.
Types of Psoriasis:
a) Psoriasis Vulgaris/Typical Psoriasis: has the typical appearanc of salmon pink plaques and silvery white scales
b) Guttate Psoriasis: involves scattered, like rain drops, small plaques; often seen in children and associated with a history of Strep throat
c) Flexural Psoriasis: disease located on the flexural surfaces of the body such as axillae, groin and submammary folds; this form is less scaly
d) Erythmodermic Psoriasis: it is a medical emergency as more than 90% of the body surface area is involved with the lesion
e) Annular Psoriasis: ring-like lesions are observed
f) Linear Psoriasis: as the name suggests, lesions are linear in pattern
g) Ungal Psoriasis (nails): general involvement of the nails only; there is pitting, ridging, discoloration (yellow, green), subungal hyperkeratosis, onycholysis and complete dystrophy of the nail is seen
h) Scalp Psoriasis: involves hair follicles, with hair loss; although hair do come back as it is non-scarring alopecia (non-cicatricial type)
i) Genital Psoriasis: involvement of the genital region with plaque formation; condition is less scaly
j) Another condition or type involves the palms and soles only
Clinical Features:
Mild itch; rash; fever is absent (only if there is secondary bacterial infection)
Pathogenesis:
It is a T-cell mediated disease involving increased keratinocyte proliferation along with inflammation and angiogenesis. There is strong association with the disease and HLA-C. The normal process of skin turnover is increased and instead of taking 24-42 days the process takes place in 3-4 days. Thus nucleated cells are seen on the surface with mitotic figures. And these 'abnormal' cells give the skin its' characteristic appearance. Tortous blood vessels in the superficial layer also give the characteristic clinical phenomenon of multiple, minute bleeding points when the scale is lifted form the plaque - Auspitz sign.
Treatment:
Drugs used to treat the condition are divided into 3 major groups:
a) Topical: include treated coal tar, salicylic acid, Resorcin, Vitamin D-3, UV B light, Tacrolimus
b) Sytemic: these include the immunosuppressant and anticancer drugs Methotrexate (MTX), Cyclosporin A and Cyclophosphamide. These drugs are highly toxic and only given in seriosu conditions and after much deliberation.
c) Both (Topical and systemic): these involve the following -
1) Steroids: oral steroids are given during erythrodermic conditions; topical are used for sensitive areas (face, genitals, flexures)
2) Retinoids: these are Vitamin A derivatives and the 2nd and 3rd generation agents, Etretinate and Acetretin respectively, are used; 1st generation agents are used for Acne treatment; these agents are systemic with Tazarotene being the topical form; all are highly teratogenic and contraception is advised upto 18 months after the therapy
3) PUVA - this is Psorolence Ultraviolet A therapy; involves administration of photoactive substance form plants which helps in alleviating the symptoms; protection of eyes and genitals throughout the day is advised.
This was a brief on Psoriasis, a condition whose pathophysiology is still being understood and is encountered in the Dermatology clinic.
Causative agents:
1) Genetic influence - positive family history; there are no specific genetic markers for the disease although it is more common for two monozygotic twins both to have the disease.
2) Autoimmune - lots of autoimmune disorders associated with the condition with a number of autoantibodies found in the serum of such patients.
3) Drug-induced - quite commonly used drugs are implicated in the condition such as antimalarials, B-adrenergic blockers, lithium and NSAIDs.
Idiopathic cause is also implicated. The condition is not curable and treatment involves palliative measures only.
Types of Psoriasis:
a) Psoriasis Vulgaris/Typical Psoriasis: has the typical appearanc of salmon pink plaques and silvery white scales
b) Guttate Psoriasis: involves scattered, like rain drops, small plaques; often seen in children and associated with a history of Strep throat
c) Flexural Psoriasis: disease located on the flexural surfaces of the body such as axillae, groin and submammary folds; this form is less scaly
d) Erythmodermic Psoriasis: it is a medical emergency as more than 90% of the body surface area is involved with the lesion
e) Annular Psoriasis: ring-like lesions are observed
f) Linear Psoriasis: as the name suggests, lesions are linear in pattern
g) Ungal Psoriasis (nails): general involvement of the nails only; there is pitting, ridging, discoloration (yellow, green), subungal hyperkeratosis, onycholysis and complete dystrophy of the nail is seen
h) Scalp Psoriasis: involves hair follicles, with hair loss; although hair do come back as it is non-scarring alopecia (non-cicatricial type)
i) Genital Psoriasis: involvement of the genital region with plaque formation; condition is less scaly
j) Another condition or type involves the palms and soles only
Clinical Features:
Mild itch; rash; fever is absent (only if there is secondary bacterial infection)
Pathogenesis:
It is a T-cell mediated disease involving increased keratinocyte proliferation along with inflammation and angiogenesis. There is strong association with the disease and HLA-C. The normal process of skin turnover is increased and instead of taking 24-42 days the process takes place in 3-4 days. Thus nucleated cells are seen on the surface with mitotic figures. And these 'abnormal' cells give the skin its' characteristic appearance. Tortous blood vessels in the superficial layer also give the characteristic clinical phenomenon of multiple, minute bleeding points when the scale is lifted form the plaque - Auspitz sign.
Treatment:
Drugs used to treat the condition are divided into 3 major groups:
a) Topical: include treated coal tar, salicylic acid, Resorcin, Vitamin D-3, UV B light, Tacrolimus
b) Sytemic: these include the immunosuppressant and anticancer drugs Methotrexate (MTX), Cyclosporin A and Cyclophosphamide. These drugs are highly toxic and only given in seriosu conditions and after much deliberation.
c) Both (Topical and systemic): these involve the following -
1) Steroids: oral steroids are given during erythrodermic conditions; topical are used for sensitive areas (face, genitals, flexures)
2) Retinoids: these are Vitamin A derivatives and the 2nd and 3rd generation agents, Etretinate and Acetretin respectively, are used; 1st generation agents are used for Acne treatment; these agents are systemic with Tazarotene being the topical form; all are highly teratogenic and contraception is advised upto 18 months after the therapy
3) PUVA - this is Psorolence Ultraviolet A therapy; involves administration of photoactive substance form plants which helps in alleviating the symptoms; protection of eyes and genitals throughout the day is advised.
This was a brief on Psoriasis, a condition whose pathophysiology is still being understood and is encountered in the Dermatology clinic.
Pericarditis
Pericardial Inflammation is usually secondary to a variety of cardiac diseases, thoracic or systemic disorders, metastases from neoplasms, or a surgical procedure on the heart. Primary pericarditis is rare and mostly of viral origin. Most evoke an acute pericarditis, but a few cause chronic infections (TB, fungi).
The common causes of Pericarditis are as follows:
a) Infectious: Viruses, pyogenic bacteria, Tuberculosis, Fungi and parasites
b) Presumed Immune causes: Rheumatic fever (RF), SLE, Scleroderma, Post MI (Dressler) syndrome and drug hypersensitivity
c) Miscellaneous: MI, uremia, post cardiac surgery, neoplasia, trauma, radiation, etc.
There are two major divisions of Pericarditis - 1) Acute and 2) Chronic
1) Acute pericarditis
There are different morphological patterns of acute inflammation of the pericardium. They are as follows:
a) Serous pericarditis - these are characteristically produced by noninfectious etiological agents such as RF, SLE, scleroderma, tumors and uremia. At times though irritation due to a bacterial infection may cause a serous effusion which may progress to serofibrinous pericarditis and ultimatively to suppurative condition. Morphologically, an inflammatory reaction is observed with scant number of WBCs. Volume of fluid is not large (50 to 100ml) and accumulation is slow. Protein content is high and specific gravity is increased as well. Rarely, organizes into fibrous adhesions.
b) Fibrinous/Serofibrinous pericarditis - these two forms are the most frequent type of pericarditis. Serous fluid mixed with fibrinous exudate is observed. Common causes include acute MI, post infarction (Dressler) syndrome (likely autoimmune), uremia, chest radiation, RF, SLE and trauma. Morphologically, surface is dry, with fine granular roughening in fibrinous pericarditis. In serofibrinous pericarditis, an increased inflammatory process is seen and there is a thicker fluid, which is yellow and cloudy because of leukocytes and erythrocytes and often fibrin. Later on, fibrin maybe digested with resolution of the exudate or it may become organized. Clinically, most striking feature is loud pericardial friction rub.
c) Suppurative pericarditis - almost invariably denotes invasion by infective organisms which reach the pericardial cavity by several routes: direct extension from neighboring inflammation; seeding from the blood; lymphatic extension; or, direct introduction during cardiotomy. Immunosuppression predisposes to the above conditions.
Morphologically, exudate ranges from thin to creamy pus of 400-500 ml of fluid. Serosal surfaces are reddened, granular and coated with the exudate. An acute inflammatory reaction is seen containing high number of neutrophils. Organization often results in the serious consequence of constrictive pericarditis. Clinically, symptoms are same as Fibrinous type with intensified constitutional symptoms like, spiking temperature, chills and fever.
d) Hemorrhagic pericarditis - Consists of exudate with blood mixed with fibrinous or suppurative effusion. It is caused most commonly by malignant neoplastic involvement of the pericardial space. Cytologic examination may reveal malignant cells. Also can be caused by Tuberculous invasion. Can be post-operative as well which can result in tamponade. Clinical sequelae similar to that of fibrinous or suppurative pericarditis.
e) Caseous pericarditis - Caseation in the pericardial sac, until proven otherwise, is tuberculous in origin. Fungal infections, although rarely, provoke similar reactions. It is the most frequent antecedent of disabling, fibrocalcific, chronic constrictive pericarditis.
2) Chronic or Healed Pericarditis
When pericarditis heals or gets organized it might simply produce fibrous thickenings of the serosal membranes (soldier's plaque), or thin, delicate adhesions of obscure origin. In other cases, organization results in complete obliteration of pericardial sac. The two types of chronic pericarditis are as follows:
a) Adhesive Mediastinopericarditis - this may follow a suppurative or caseous pericarditis, previous cardiac surgery or irradiation to mediastinum. Pericardial sac is obliterated, and adherence to the external surfaces of the parietal layer produces great strain on cardiac function. The increased workload causes cardiac hypertrophy and dilation, mimicking DCM (Dilated Cardiomyopathy).
b) Constrictive Pericarditis - heart is enclosed in a dense, fibrous or fibrocalcific scar that limits diastolic expansion and seriously restricts cardiac output, resembling restrictive cardiomyopathy. Pericardial space is obliterated and heart surrounded by dense, adherent layer of scar that can resemble a plaster mold in extreme cases (concretio cordis).
Signs may resemble the above form of chronic disease but signs of hypertrophy and DCM are absent as heart is enclosed in a fibrous 'case' and hence there is a quiet heart with reduced output. Major therapy is removal of the shell of the constricting fibrous tissue (pericardiotomy).
The common causes of Pericarditis are as follows:
a) Infectious: Viruses, pyogenic bacteria, Tuberculosis, Fungi and parasites
b) Presumed Immune causes: Rheumatic fever (RF), SLE, Scleroderma, Post MI (Dressler) syndrome and drug hypersensitivity
c) Miscellaneous: MI, uremia, post cardiac surgery, neoplasia, trauma, radiation, etc.
There are two major divisions of Pericarditis - 1) Acute and 2) Chronic
1) Acute pericarditis
There are different morphological patterns of acute inflammation of the pericardium. They are as follows:
a) Serous pericarditis - these are characteristically produced by noninfectious etiological agents such as RF, SLE, scleroderma, tumors and uremia. At times though irritation due to a bacterial infection may cause a serous effusion which may progress to serofibrinous pericarditis and ultimatively to suppurative condition. Morphologically, an inflammatory reaction is observed with scant number of WBCs. Volume of fluid is not large (50 to 100ml) and accumulation is slow. Protein content is high and specific gravity is increased as well. Rarely, organizes into fibrous adhesions.
b) Fibrinous/Serofibrinous pericarditis - these two forms are the most frequent type of pericarditis. Serous fluid mixed with fibrinous exudate is observed. Common causes include acute MI, post infarction (Dressler) syndrome (likely autoimmune), uremia, chest radiation, RF, SLE and trauma. Morphologically, surface is dry, with fine granular roughening in fibrinous pericarditis. In serofibrinous pericarditis, an increased inflammatory process is seen and there is a thicker fluid, which is yellow and cloudy because of leukocytes and erythrocytes and often fibrin. Later on, fibrin maybe digested with resolution of the exudate or it may become organized. Clinically, most striking feature is loud pericardial friction rub.
c) Suppurative pericarditis - almost invariably denotes invasion by infective organisms which reach the pericardial cavity by several routes: direct extension from neighboring inflammation; seeding from the blood; lymphatic extension; or, direct introduction during cardiotomy. Immunosuppression predisposes to the above conditions.
Morphologically, exudate ranges from thin to creamy pus of 400-500 ml of fluid. Serosal surfaces are reddened, granular and coated with the exudate. An acute inflammatory reaction is seen containing high number of neutrophils. Organization often results in the serious consequence of constrictive pericarditis. Clinically, symptoms are same as Fibrinous type with intensified constitutional symptoms like, spiking temperature, chills and fever.
d) Hemorrhagic pericarditis - Consists of exudate with blood mixed with fibrinous or suppurative effusion. It is caused most commonly by malignant neoplastic involvement of the pericardial space. Cytologic examination may reveal malignant cells. Also can be caused by Tuberculous invasion. Can be post-operative as well which can result in tamponade. Clinical sequelae similar to that of fibrinous or suppurative pericarditis.
e) Caseous pericarditis - Caseation in the pericardial sac, until proven otherwise, is tuberculous in origin. Fungal infections, although rarely, provoke similar reactions. It is the most frequent antecedent of disabling, fibrocalcific, chronic constrictive pericarditis.
2) Chronic or Healed Pericarditis
When pericarditis heals or gets organized it might simply produce fibrous thickenings of the serosal membranes (soldier's plaque), or thin, delicate adhesions of obscure origin. In other cases, organization results in complete obliteration of pericardial sac. The two types of chronic pericarditis are as follows:
a) Adhesive Mediastinopericarditis - this may follow a suppurative or caseous pericarditis, previous cardiac surgery or irradiation to mediastinum. Pericardial sac is obliterated, and adherence to the external surfaces of the parietal layer produces great strain on cardiac function. The increased workload causes cardiac hypertrophy and dilation, mimicking DCM (Dilated Cardiomyopathy).
b) Constrictive Pericarditis - heart is enclosed in a dense, fibrous or fibrocalcific scar that limits diastolic expansion and seriously restricts cardiac output, resembling restrictive cardiomyopathy. Pericardial space is obliterated and heart surrounded by dense, adherent layer of scar that can resemble a plaster mold in extreme cases (concretio cordis).
Signs may resemble the above form of chronic disease but signs of hypertrophy and DCM are absent as heart is enclosed in a fibrous 'case' and hence there is a quiet heart with reduced output. Major therapy is removal of the shell of the constricting fibrous tissue (pericardiotomy).
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that most commonly causes inflammation and tissue damage in joints (arthritis) and tendon sheaths, together with anemia. It can also produce diffuse inflammation in the lungs, pericardium, pleura, and the sclera of the eye, and also nodular lesions, most common in subcutaneous tissue under the skin. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility. It is diagnosed chiefly on symptoms and signs, but also with blood tests (especially a test called rheumatoid factor) and X-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues.
Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur.
Joints:
The arthritis of rheumatoid arthritis is due to synovitis, which is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness prevents their use. With time, RA nearly always affects multiple joints (it is a polyarthritis). Most commonly, small joints of the hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity.
Skin:
The rheumatoid nodule, which is often subcutaneous, is the feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both.
Lungs (fibrosis), kidneys (amyloidosis), heart (atherosclerosis, MI, stroke, pericarditis) and blood vessels (vasculitis) are also involved.
Diagnosis
X-rays:
X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, these may not show any changes in the early stages of the disease, but more advanced cases demonstrate erosions and bone resorption.
Blood tests:
When RA is clinically suspected, immunological studies are required, such as testing for the presence of rheumatoid factor (RF, a specific antibody). A negative RF does not rule out RA; rather, the arthritis is called seronegative. This is the case in about 15% of patients.
Because of this low specificity, a new serological test has been developed, which tests for the presence of so called anti-citrullinated protein antibodies (ACPAs). Like RF, this test is positive in only a proportion (67%) of all RA cases, but is rarely positive if RA is not present, giving it a specificity of around 95%.
Diagnostic criteria
The American College of Rheumatology has defined (1987) the following criteria for the classification of rheumatoid arthritis:
• Morning stiffness of >1 hour most mornings for at least 6 weeks.
• Arthritis and soft-tissue swelling of >3 of 14 joints/joint groups, present for at least 6 weeks
• Arthritis of hand joints, present for at least 6 weeks
• Symmetric arthritis, present for at least 6 weeks
• Subcutaneous nodules in specific places
• Rheumatoid factor at a level above the 95th percentile
• Radiological changes suggestive of joint erosion
At least four criteria have to be met for classification as RA.
Pathophysiology
Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.
The key pieces of evidence relating to pathogenesis are:
1. A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cell-associated protein PTPN22.
2. A link with cigarette smoking that appears to be causal.
3. A dramatic response in many cases to blockade of the cytokine TNF (alpha).
4. A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes.
5. A more or less random pattern of whether and when predisposed individuals are affected.
6. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA).
These data suggest that the disease involves abnormal B cell - T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random) epidemiology suggests that the rate limiting step in genesis of disease in predisposed individuals may be an inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation.
Treatment
There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process.
The goal of treatment is two-fold:
1) Alleviating the current symptoms, and
2) Preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked.
Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone can also have an important benefit if added to a proper specific anti-rheumatic treatment.
Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics. Treatment also includes rest and physical activity.
This is a brief article on Rheumatoid Arthritis. Some of the specifics regarding treatment will be presented in future articles on those topics (DMARDS, Pathology, etc.)
Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur.
Joints:
The arthritis of rheumatoid arthritis is due to synovitis, which is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness prevents their use. With time, RA nearly always affects multiple joints (it is a polyarthritis). Most commonly, small joints of the hands, feet and cervical spine are affected, but larger joints like the shoulder and knee can also be involved, differing per individual. As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity.
Skin:
The rheumatoid nodule, which is often subcutaneous, is the feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both.
Lungs (fibrosis), kidneys (amyloidosis), heart (atherosclerosis, MI, stroke, pericarditis) and blood vessels (vasculitis) are also involved.
Diagnosis
X-rays:
X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, these may not show any changes in the early stages of the disease, but more advanced cases demonstrate erosions and bone resorption.
Blood tests:
When RA is clinically suspected, immunological studies are required, such as testing for the presence of rheumatoid factor (RF, a specific antibody). A negative RF does not rule out RA; rather, the arthritis is called seronegative. This is the case in about 15% of patients.
Because of this low specificity, a new serological test has been developed, which tests for the presence of so called anti-citrullinated protein antibodies (ACPAs). Like RF, this test is positive in only a proportion (67%) of all RA cases, but is rarely positive if RA is not present, giving it a specificity of around 95%.
Diagnostic criteria
The American College of Rheumatology has defined (1987) the following criteria for the classification of rheumatoid arthritis:
• Morning stiffness of >1 hour most mornings for at least 6 weeks.
• Arthritis and soft-tissue swelling of >3 of 14 joints/joint groups, present for at least 6 weeks
• Arthritis of hand joints, present for at least 6 weeks
• Symmetric arthritis, present for at least 6 weeks
• Subcutaneous nodules in specific places
• Rheumatoid factor at a level above the 95th percentile
• Radiological changes suggestive of joint erosion
At least four criteria have to be met for classification as RA.
Pathophysiology
Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.
The key pieces of evidence relating to pathogenesis are:
1. A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cell-associated protein PTPN22.
2. A link with cigarette smoking that appears to be causal.
3. A dramatic response in many cases to blockade of the cytokine TNF (alpha).
4. A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes.
5. A more or less random pattern of whether and when predisposed individuals are affected.
6. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA).
These data suggest that the disease involves abnormal B cell - T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random) epidemiology suggests that the rate limiting step in genesis of disease in predisposed individuals may be an inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation.
Treatment
There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process.
The goal of treatment is two-fold:
1) Alleviating the current symptoms, and
2) Preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked.
Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable. However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone can also have an important benefit if added to a proper specific anti-rheumatic treatment.
Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics. Treatment also includes rest and physical activity.
This is a brief article on Rheumatoid Arthritis. Some of the specifics regarding treatment will be presented in future articles on those topics (DMARDS, Pathology, etc.)
Lower Abdominal Pain
Lower Abdominal Pain - Differential Diagnoses
Lower Abdominal pain may signify a number of diseases and these include the following:
a. Appendicitis
b. Crohn's Disease
c. Carcinoma of caecum and right colon
d. Diverticulitis
e. Carcinoma of left colon/rectum
f. Pelvic Inflammatory Disease
The major symptoms and signs of these conditions are as follows:
a. Appendicitis
Major Symptoms - vague pain beginning in the centre of abdomen; shifts to right iliac fossa in 2 to 3 days and becomes severe; loss of appetite usual; nausea and slight vomitting; constipation is reported prior to the pain, though sometimes diarrhoea might be experienced; acute appendicitis might also present with symptoms of lower bowel obstruction
Major Signs - patient looks unwell; low-grade pyrexia might be present; pulse rate is increased and rises with the spread of infection; tongue is furred, with typical foeter oris present;
right iliac fossa is tender with pain maximal at McBurney's point; the muscles around it guard; Rovsing's sign is positive; extension of right hip joint might cause pain if appendix is retro-caecal
b. Crohn's Disease
Major Symptoms - are similar to those of acute appendicitis; thickened terminal ileum might be felt in the RIF; distinguishing symptom is recurrent episodes of diarrhoea in weeks before acute attack; long history of colicky central or lower abdominal pain
Major Signs- anal complications - abcesses and fistulae - are common; there may be other signs of chronic inflammatory disease like finger clubbing, erythema nodosum, sacro-illitis, episcleritis, pyoderma, gangreosum, anal sepsis, sclerosing cholangitis, gallstones and renal stones;
c. Carcinoma of caecum and right colon
Major Symptoms - anaemia; weight loss; mass; pain might be dull or colicky in the RIF;
Major Signs - abdomen generally distended; RIF tender; some guarding muscles; firm, irregular mass might be felt in the RIF or right lumbar region; may be fixed or freely mobile; liver may be palpable, enalrged or irregular; mass is dull to percuss; bowel sounds normal unless obstructed or peritonitis present; occult blood maybe present in the faeces
d. Diverticulitis
Major Symptoms - first symptom is mild intermittent lower abdominal pain which shifts to the left iliac fossa; it becomes a constant ache and intensifies with time; nausea and loss of appetite; most are constipated, some have diarrhoea; if bladder is inflamed, there is increased frequency and painful micturition; there might be a history of chronic diverticular disease, flatulence, distension LIF pain
Major Signs - patients lie still because of pain; flushed; usually pyrexic w/tachycardia; tenderness and guarding in the LIF; there may be a palpable, sausage-shaped mass; Rovsing's sign might be positive; rebound tenderness + ve if generalized peritonitis; pain experienced on rectal examination if finger pushed on left side
e. Carcinoma of left colon
Major Symptoms - pain is rare, usually mild lower abdomen colic; alternating constipation and diarrhoea - typical of annular variety of left colon cancer; weight loss often precedes anorexia; rectal bleeding not common, but when occurs is dark and plum-coloured; recto-sigmoid tumors usually bleed
Major Signs - weight loss may be apparent; in thin patients there may be a swelling in the LIF; mass might be tender if surrounding area is inflamed; liver may be palpable, irregular surface and edge; mass in LIF dull to percussion; loud, high-pitched continous gurglings can be heard during attacks of colic; tumor in apex of loop of sigmoid colon is palpable on bimanual exam; blood may be visible on fingerstall
f. Pelvic Inflammatory Disease
Major Symptoms - infection in one or both fallopian tubes and associated with infection in surrounding tissue, hence the term Pelvic Inflammatory Disease; purulent yellow-white vaginal discharge precedes gradual lower abdominal pain by a few days; pain is constant and can become severe; may radiate to lower part of back; menstruation preceding the pain may be irregular and a history of dysmenorrhoea; sweating and rigors are common; painful micturition also common
Major Signs - flushed and feverish; tenderness and some guarding present; tenderness often bilateral; huge pyosalpinx occasionally palpable; vaginal intortus reveals yellow-white discharge - should be sent for culture; speculum exam may demonstrate pus coming from cervical canal
Some other diseases also cause lwer abdominal pain as do hernias, but the above are the major diseases related to the GIT which cause lower abdominal pain.
Lower Abdominal pain may signify a number of diseases and these include the following:
a. Appendicitis
b. Crohn's Disease
c. Carcinoma of caecum and right colon
d. Diverticulitis
e. Carcinoma of left colon/rectum
f. Pelvic Inflammatory Disease
The major symptoms and signs of these conditions are as follows:
a. Appendicitis
Major Symptoms - vague pain beginning in the centre of abdomen; shifts to right iliac fossa in 2 to 3 days and becomes severe; loss of appetite usual; nausea and slight vomitting; constipation is reported prior to the pain, though sometimes diarrhoea might be experienced; acute appendicitis might also present with symptoms of lower bowel obstruction
Major Signs - patient looks unwell; low-grade pyrexia might be present; pulse rate is increased and rises with the spread of infection; tongue is furred, with typical foeter oris present;
right iliac fossa is tender with pain maximal at McBurney's point; the muscles around it guard; Rovsing's sign is positive; extension of right hip joint might cause pain if appendix is retro-caecal
b. Crohn's Disease
Major Symptoms - are similar to those of acute appendicitis; thickened terminal ileum might be felt in the RIF; distinguishing symptom is recurrent episodes of diarrhoea in weeks before acute attack; long history of colicky central or lower abdominal pain
Major Signs- anal complications - abcesses and fistulae - are common; there may be other signs of chronic inflammatory disease like finger clubbing, erythema nodosum, sacro-illitis, episcleritis, pyoderma, gangreosum, anal sepsis, sclerosing cholangitis, gallstones and renal stones;
c. Carcinoma of caecum and right colon
Major Symptoms - anaemia; weight loss; mass; pain might be dull or colicky in the RIF;
Major Signs - abdomen generally distended; RIF tender; some guarding muscles; firm, irregular mass might be felt in the RIF or right lumbar region; may be fixed or freely mobile; liver may be palpable, enalrged or irregular; mass is dull to percuss; bowel sounds normal unless obstructed or peritonitis present; occult blood maybe present in the faeces
d. Diverticulitis
Major Symptoms - first symptom is mild intermittent lower abdominal pain which shifts to the left iliac fossa; it becomes a constant ache and intensifies with time; nausea and loss of appetite; most are constipated, some have diarrhoea; if bladder is inflamed, there is increased frequency and painful micturition; there might be a history of chronic diverticular disease, flatulence, distension LIF pain
Major Signs - patients lie still because of pain; flushed; usually pyrexic w/tachycardia; tenderness and guarding in the LIF; there may be a palpable, sausage-shaped mass; Rovsing's sign might be positive; rebound tenderness + ve if generalized peritonitis; pain experienced on rectal examination if finger pushed on left side
e. Carcinoma of left colon
Major Symptoms - pain is rare, usually mild lower abdomen colic; alternating constipation and diarrhoea - typical of annular variety of left colon cancer; weight loss often precedes anorexia; rectal bleeding not common, but when occurs is dark and plum-coloured; recto-sigmoid tumors usually bleed
Major Signs - weight loss may be apparent; in thin patients there may be a swelling in the LIF; mass might be tender if surrounding area is inflamed; liver may be palpable, irregular surface and edge; mass in LIF dull to percussion; loud, high-pitched continous gurglings can be heard during attacks of colic; tumor in apex of loop of sigmoid colon is palpable on bimanual exam; blood may be visible on fingerstall
f. Pelvic Inflammatory Disease
Major Symptoms - infection in one or both fallopian tubes and associated with infection in surrounding tissue, hence the term Pelvic Inflammatory Disease; purulent yellow-white vaginal discharge precedes gradual lower abdominal pain by a few days; pain is constant and can become severe; may radiate to lower part of back; menstruation preceding the pain may be irregular and a history of dysmenorrhoea; sweating and rigors are common; painful micturition also common
Major Signs - flushed and feverish; tenderness and some guarding present; tenderness often bilateral; huge pyosalpinx occasionally palpable; vaginal intortus reveals yellow-white discharge - should be sent for culture; speculum exam may demonstrate pus coming from cervical canal
Some other diseases also cause lwer abdominal pain as do hernias, but the above are the major diseases related to the GIT which cause lower abdominal pain.
Wednesday, January 7, 2009
50 year old overweight patient with severe dyspnea
A 50 year old man comes to your clinic with complaints of severe dyspnea associated with fever. History reveals that he is a chronic smoker for 30 years and has productive cough for several years. Physical examination reveals an enlarged chest diameter, generalized edematous state, overweight and cyanotic lips. Radiological findings show a long and narrow heart, hyperlucent lung fields with evident hyperinflation, and no infiltrates.
Diagnosis: COPD (Chronic Obstructive Pulmonary Disease)
Diagnosis: COPD (Chronic Obstructive Pulmonary Disease)
- COPD is commonly caused by inhalation of cigarette smoking; can be hereditary due to alpha-antitrypsin deficiency
- Blue bloater
- Chronic bronchitis
- Overweight
- Edematous
- Cyanotic
- Chronic bronchitis involves hypersecretion of mucus and enlarged submucous glands of the large airways, causing chronic productive cough.
- Histology reveals mucus plugging of the bronchioles, pigmented alveolar macrophages, and fibrosis of the bronchiolar wall.
- Spirometry and flow volume loops help to identify the type of lung disease (Restrictive Vs. Obstructive).
- Manage the patient with bronchodilators by hand-held nebulizers, glucocorticoids and antibiotics (if there is an underlying respiratory infection). Controlled oxygen administration with nasal oxygen can help correct hypoxemia and reduce mortality.
- Patients should also be advice to get pneumococcal immunization and annual influenza vaccination.
- Bronchiectasis
- Bronchitis
- Emphysema
- Chronic asthma
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