Gout is an important topic for all 3 USMLE steps. Below is a summary of key potential facts that may be questioned in these exams with regards to the treatment of Gout.
Treatment of Acute Attacks of Gout
-First the diagnosis should be confirmed. Septic arthritis has the potential to look exactly like gout, hence the initial step is always arthrocentesis unless the patient has a known diagnosis.
-Next step is pain management. Nonsteroidal anti-inflammatory drugs (NSAIDs), colchicine, and ACTH are the mainstays of treatment. Co-existent health conditions determine which drugs are used. For example renal failure may contraindicate use of certain NSAIDS.
-When comorbidities limit the use of NSAIDs or colchicine, intra-articular steroid injection may be indicated.
-One must remember that control of the underlying hyperuricemia is contraindicated until the acute attack is controlled as it may intensify and prolong the attack. However if the patient is already on allopurinol or probenecid, they should be continued.
Medications for acute gout:
Nonsteroidal anti-inflammatory drugs
NSAIDs are the first drugs of choice in most patients (typically indomethacin is used except in elderly because of CNS adverse effects). Contraindications to NSAIDS use include peptic ulcer disease or GI bleeding, renal failure, abnormal liver function and patients on warfarin (selective COX-2 inhibitors like celecoxib can be used). Additional caution in needed for those patients who are on ACE inhibitors as both ACE inhibitors and NSAIDS can decrease the GFR. NSAIDS are given at full dose for about 4-5 days and then dose is gradually decreased.
Colchicine
Colchicine is a mitotic inhibitor and has now become a second line treatment because of risk of adverse effects. To be effective colchicine therapy must be initiated within 24 hours of onset of the acute attack. Common adverse effects include diarrhea and vomiting, in 80% of patients. A number of dosing regimens are proposed with recent recommendations favoring lower doses with a maximum of 2.5 mg/24 hours and 6 mg over 4 days. Contraindication to colchicine include severe renal insufficiency (GFR less than 10 mL/min), hepatic dysfunction and biliary obstruction.
Colchicine is one agent that can be used in acute gout as well as for Gout prophylaxis (0.6mg BID). Myopathy is an important side effect of chronic colchicine therapy.
Corticosteroids
Corticosteroids can be given to patients with gout who cannot use NSAIDs or colchicine, but ACTH is generally preferred over steroids.
Treatment of Chronic Gout
-Firstly attempt should be made at avoiding the use of medications that elevate uric acid. For example thiazides should be avoided and losartan should be considered in stead. (Losartan is uricosuric at 50 mg/day doses). If the patient has tophaceous disease, probenecid should not be used.
-Probenecid (uricosuric agent) and allopurinol (decrease production of uric acid) are the two main drugs used. Probenecid is preferred by some.
-Patients with very high uric acid excretion will benefit from Allopurinol. It is also the drug of choice in patients with existing renal disease.
Medications for chronic gout:
Probenecid
Probenecid inhibits tubular reabsorption of uric acid. Some physicians recommend alkalizing the urine when starting probenecid to reduce the risk for renal stone formation. All patients should be advised to drink plenty of liquids (>2L a day).
Allopurinol
Allopurinol is xanthine oxidase inhibitor and thus reduces the generation of uric acid. Therefore, it should be used in patients who overproduce uric acid (also used in patients at risk of tumor lysis syndrome). Common side effects include dyspepsia, headache, diarrhea, and rash. Allopurinol hypersensitivity is a wellknown but rare complication with high mortality. Allopurinol is also associated with the drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. For these reasons Allopurinol should be discontinued in patients who develop a rash.
Febuxostat
Febuxostat is a newer nonpurine selective inhibitor of xanthine oxidase, and is a potential alternative to allopurinol.
Other treatments:
Rasburicase
Rasburicase is an extremely potent (and expensive) drug that can metabolize uric acid into soluble substances. It is used in treatment of tumor lysis syndrome. It is very prone to causing allergic reaction and its role in treatment of gout is not clear.
Diet and Activity
Foods very high in purines include hearts, sweetbreads (eg, pancreas, thymus), smelt, sardines, mussels, anchovies, trout, haddock, scallops, mutton, veal, liver, bacon, salmon, kidneys, and turkey. These should be avoided as much as possible. Patients with gout should limit alcohol as it can precipitate gout. This is especially true for beer and hard alcohol but mild-moderate wine drinking is well tolerated by most.
Increasing dairy intake, folic acid intake, and coffee consumption may reduce gout flares. Weight reduction in patients who are obese can improve hyperuricemia.
Showing posts with label Rheumatology. Show all posts
Showing posts with label Rheumatology. Show all posts
Systemic Lupus Erythematosus (SLE) Nephritis Classes and Prognosis
Class I has no histologic changes and
has the best prognosis.
Class II has proliferation in the
mesangium and has good prognosis.
Class III has focal proliferation. It
has variable prognosis.
Class IV has diffuse proliferation and
bad prognosis.
Class V has membranous changes and
relatively better progrnosis.
Class VI has scarred glomeruli and end
stage disease.
This letter M has five red circles. (Membranous)
Kawasaki Disease
Diagnostic Criteria for Kawasaki
Presence of fever for at least 5 days and at least four of five criteria:
- Bilateral conjunctival injection without exudate
- Polymorphous rash
- Changes in lips and mouth (Reddened, dry, or cracked lips, Strawberry tongue, Diffuse redness of oral cavity or pharynx)
- Changes in extremities (Reddening of palms or soles, Indurative edema of hands or feet, Desquamation of skin of hands, feet, and groin (in convalescence)
- Cervical lymphadenopathy (More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful)
- Bilateral conjunctival injection without exudate
- Polymorphous rash
- Changes in lips and mouth (Reddened, dry, or cracked lips, Strawberry tongue, Diffuse redness of oral cavity or pharynx)
- Changes in extremities (Reddening of palms or soles, Indurative edema of hands or feet, Desquamation of skin of hands, feet, and groin (in convalescence)
- Cervical lymphadenopathy (More than 15 mm in diameter, usually unilateral, single, non-purulent, and painful)
Exclusion of other conditions with similar clinical picture like:
Staphylococcal scalded skin syndrome, toxic shock syndrome
Scarlet fever
Stevens-Johnson syndrome
Drug reaction
Juvenile rheumatoid arthritis
Sjogren's Syndrome
Revised International Classification Criteria for Sjögren's Syndrome
I. Ocular symptoms: Yes to one or more of the following:
Have you had daily, persistent, troublesome dry eyes for more than 3 months?
Do you have a recurrent sensation of sand or gravel in the eyes?
Do you use tear substitutes more than 3 times a day?
II. Oral symptoms: Yes to one or more of the following:
Have you had a daily feeling of dry mouth for more than 3 months?
Have you had recurrently or persistently swollen salivary glands as an adult?
Do you frequently drink liquids to aid in swallowing dry food?
III. Ocular signs- objective evidence of ocular involvement defined as a positive result for at least one of the following two tests:
Schirmer's I test, performed without anaesthesia (
Rose bengal score or other ocular dye score (>/=4 according to van Bijsterveld's scoring system)
IV. Histopathology: Focal lymphocytic sialoadenitis in minor salivary glands. Requires a focus score >/=1, defined as a number of lymphocytic foci (which are adjacent to normal-appearing mucous acini and contain more than 50 lymphocytes) per 4 mm2 of glandular tissue
V. Salivary gland involvement: objective evidence of salivary gland involvement defined by a positive result for at least one of the following diagnostic tests:
Unstimulated whole salivary flow (
Parotid sialography showing the presence of diffuse sialectasias (punctate, cavitary or destructive pattern), without evidence of obstruction in the major ducts
Salivary scintigraphy showing delayed uptake, reduced concentration and/or delayed excretion of tracer
VI. Autoantibodies: presence in the serum of the following autoantibodies:
Antibodies to Ro(SSA) or La(SSB) antigens, or both
Classification
Primary Sjogren's Syndrome
In patients without any potentially associated disease, primary SS may be defined as follows
1. The presence of any 4 of the 6 items is indicative of primary SS, as long as either item IV (Histopathology) or VI (Serology) is positive
2. The presence of any 3 of the 4 objective criteria items (that is, items III, IV, V, VI)
3. The classification tree procedure represents a valid alternative method for classification, although it should be more properly used in clinical-epidemiological survey
Secondary Sjogren's Syndrome
In patients with a potentially associated disease (for instance, another well defined connective tissue disease), the presence of item I or item II plus any 2 from among items III, IV, and V may be considered as indicative of secondary SS
Must exclude:
Past head and neck radiation treatment
Hepatitis C
Acquired immunodeficiency disease
Pre-existing lymphoma
Sarcoidosis
Graft versus host disease
Use of anticholinergic drugs
Polymyalgia Rheumatica
Diagnostic Criteria for Polymyalgia Rheumatica
Bird's or Wood's criteria
Presence of three or more of the following, or at least one of the following plus positive results on temporal artery biopsy:
Bilateral shoulder pain and/or stiffness
Less than two weeks from onset of symptoms to maximal symptoms
ESR greater than 40 mm per hour
Morning stiffness lasting longer than one hour
Patient older than 65 years
Depression and/or weight loss
Bilateral upper arm tenderness
Jones and Hazleman's criteria
Presence of all of the following:
Shoulder and pelvic girdle muscle pain without weakness
Morning stiffness
Symptom duration of more than two months unless treated
ESR greater than 30 mm per hour or C-reactive protein level greater than 6 mg per L
No rheumatoid arthritis, inflammatory arthritis or malignant neoplasm
No objective signs of muscle disease
Prompt and dramatic response to systemic corticosteroid therapy
SLE Criteria/American College of Rheumatology 1982 revised criteria for lupus
Any 4 or more of the 11 criteria are required to classify a patient as having SLE. These criteria do not have to be present all at once.
Malar rash: Fixed erythema, flat, or raised, over the malar eminences, characteristic sparing of the nasolabial folds.
Discoid rash: Erythematous raised patches with adherent keratotic scaling with or without plugging of the follicles; scarring may occur in older lesions.
Photosensitivity
Oral ulcers: Usually painless, Have to be observed by physician. History of ulcers is not sufficient.
Arthritis: Usually nonerosive arthritis
Serositis(inflammation of visceral membranes): Pleuritis or Pericarditis.
Renal involement: Persistent proteinuria >0.5 g/day or >3+ if quantification not performed OR Cellular casts.
Brain involvement: Seizures OR Psychosis.
Hematologic disorder: Hemolytic anemia OR Leukopenia: <4000/mm^3 on ≥2 occasions OR Lymphopenia: <1500/mm^3 on ≥2 occasions OR Thrombocytopenia: <100,000/mm^3.
Immunologic disorder:
Anti-DNA antibody
Anti-Smith antibody
Antiphospholipid antibodies based on:
- increased level of IgG or IgM anticardiolipin antibodies
-positive lupus anticoagulant
-A false-positive serologic test for syphilis
Antinuclear antibody:
An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome.
Malar rash: Fixed erythema, flat, or raised, over the malar eminences, characteristic sparing of the nasolabial folds.
Discoid rash: Erythematous raised patches with adherent keratotic scaling with or without plugging of the follicles; scarring may occur in older lesions.
Photosensitivity
Oral ulcers: Usually painless, Have to be observed by physician. History of ulcers is not sufficient.
Arthritis: Usually nonerosive arthritis
Serositis(inflammation of visceral membranes): Pleuritis or Pericarditis.
Renal involement: Persistent proteinuria >0.5 g/day or >3+ if quantification not performed OR Cellular casts.
Brain involvement: Seizures OR Psychosis.
Hematologic disorder: Hemolytic anemia OR Leukopenia: <4000/mm^3 on ≥2 occasions OR Lymphopenia: <1500/mm^3 on ≥2 occasions OR Thrombocytopenia: <100,000/mm^3.
Immunologic disorder:
Anti-DNA antibody
Anti-Smith antibody
Antiphospholipid antibodies based on:
- increased level of IgG or IgM anticardiolipin antibodies
-positive lupus anticoagulant
-A false-positive serologic test for syphilis
Antinuclear antibody:
An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome.
Chronic Fatigue Syndrome
Onset may be acute or subacute.
It is essentially a diagnosis of exclusion.
The 1994 CDC diagnostic criteria require the concurrent presence of at least 4 of the following symptoms over a 6-month period:
Impaired short-term memory or concentration
Sore throat
Tender lymph nodes/glands
Muscular pain
Joint stiffness in multiple areas
New-onset headaches
Unrefreshing sleep
Postexertional fatigue/malaise lasting more than 24 hours.
Treatments:
-Exercise
-Cognitive behavioral therapy
The syndrome is associated with depression, obstructive sleep apnea and other psychiatric illnesses.
It is essentially a diagnosis of exclusion.
The 1994 CDC diagnostic criteria require the concurrent presence of at least 4 of the following symptoms over a 6-month period:
Impaired short-term memory or concentration
Sore throat
Tender lymph nodes/glands
Muscular pain
Joint stiffness in multiple areas
New-onset headaches
Unrefreshing sleep
Postexertional fatigue/malaise lasting more than 24 hours.
Treatments:
-Exercise
-Cognitive behavioral therapy
The syndrome is associated with depression, obstructive sleep apnea and other psychiatric illnesses.
Fibromyalgia
The following points help make diagnosis:
-Women
-Chronic, widespread body pain
-Fatigue, stiffness, and unrefreshing sleep.
->11 of 18 defined tender points are tender on palpation.
Treatment of choice is patient education, graded exercise, and behavioral therapy.
Tricyclic antidepressants may be helpful.
-Women
-Chronic, widespread body pain
-Fatigue, stiffness, and unrefreshing sleep.
->11 of 18 defined tender points are tender on palpation.
Treatment of choice is patient education, graded exercise, and behavioral therapy.
Tricyclic antidepressants may be helpful.
Primary Amyloidosis- Types, proteins and clinical associations
| Type | Deposited Protein | Clinical Associations |
| Systemic | Immunoglobulin lambda chains | Multiple myeloma |
| Transthyretin | Familial amyloidosis, senile cardiac amyloidosis | |
| Amyloidosis – A protein | Inflammation-associated amyloidosis | |
| Beta2 -microglobulin | Dialysis-related amyloidosis | |
| Immunoglobulin heavy chains | Systemic amyloidosis | |
| Hereditary | Fibrinogen alpha chain, Apo A1 and Apo A2 | Familial systemic amyloidosis |
| Lysozyme | Familial systemic amyloidosis | |
| Central nervous system | Beta protein precursor | Alzheimer's |
| Prion protein | Creutzfeldt-Jakob disease, Gerstmann-Strãussler-Scheinker disease, fatal familial insomnia | |
| Cystatin C | hereditary cerebral hemorrhage with amyloidosis (Icelandic) | |
| Ocular | Gelsolin | Familial amyloidosis (Finnish) |
| Lactoferrin | Familial corneal amyloidosis | |
| Keratoepithelin | Familial corneal dystrophies | |
| Localized | Calcitonin | Thyroid Carcinoma (Medullary) |
| Amylin | Insulinoma, type 2 diabetes | |
| Atrial natriuretic factor amyloid | Isolated atrial amyloidosis | |
| Prolactin | Pituitary amyloid | |
| Keratin | Cutaneous amyloidosis | |
| Medin | Aortic amyloidosis in elderly people |
Juvenile rheumatoid arthritis (JRA) - Classification and epidemiology
JRA (Now also called Juvenile idiopathic arthritis or JIA) is one of the most common chronic joint disorders in kids. It is classified as follows.
1) Pauciarticular disease: (About 50% of all JRA cases) Less than 5 joints are involved. Usually large joints, such as the shoulder, elbow, hip, and knee are affected. Pauciarticular JRA is most common in kids younger than 8 years. There is 20-30% chance of developing iridocyclitis.
2) Polyarticular disease: (30% of all JRA cases) As the name suggests this type affects more than 5 joints. Unlike the pauciarticular type small joints such as those in the hands and feet are often involved.
3) Systemic onset JRA (a.k.a Stills disease, 20% of all JRA). Children present with high fevers, skin rashes, and joint pain. Acute leukemia must be excluded as it can present identically.
1) Pauciarticular disease: (About 50% of all JRA cases) Less than 5 joints are involved. Usually large joints, such as the shoulder, elbow, hip, and knee are affected. Pauciarticular JRA is most common in kids younger than 8 years. There is 20-30% chance of developing iridocyclitis.
2) Polyarticular disease: (30% of all JRA cases) As the name suggests this type affects more than 5 joints. Unlike the pauciarticular type small joints such as those in the hands and feet are often involved.
3) Systemic onset JRA (a.k.a Stills disease, 20% of all JRA). Children present with high fevers, skin rashes, and joint pain. Acute leukemia must be excluded as it can present identically.
Churg-Strauss Syndrome (CSS)
CSS was first described in 1951 by Jacob Churg and Lotte Strauss as a symptom complex with asthma, eosinophilia and vasculitis. CSS resembles polyarteritis nodosa (PAN) in many aspects. CSS however has characteristic granulomas while PAN does not.(Hence also called allergic granulomatosis).
CSS occurs in middle aged individuals. They present with new or worse asthma. Asthma can start many years before the other symptoms.
Marked by eosinophilia then follows. After that there is the phase vasculitis. Vasculitis can involve the lungs, skin, nerves, kidneys and sometimes other body organs.
CSS occurs in middle aged individuals. They present with new or worse asthma. Asthma can start many years before the other symptoms.
Marked by eosinophilia then follows. After that there is the phase vasculitis. Vasculitis can involve the lungs, skin, nerves, kidneys and sometimes other body organs.
Ankylosing Spondylitis (AS)
Characteristic symptoms of AS include back pain that is worst in the morning and improves with exercise. AS is more common in men, and patients usually present at a younger age (18-35 years) relative to patients with mechanical causes of back pain or arthritis.
AS is a clinical diagnosis, HLA B27 testing is positive in a large proportion of patients with AS but one should keep in mind that in the general population, about 8% Caucasian, 4% African, 2-9% Chinese, and 0.1-0.5% Japanese have the HLA-B27 antigen.
Commonest cause of death related to AS is renal failure secondary to amyloidosis in AS.
AS is a clinical diagnosis, HLA B27 testing is positive in a large proportion of patients with AS but one should keep in mind that in the general population, about 8% Caucasian, 4% African, 2-9% Chinese, and 0.1-0.5% Japanese have the HLA-B27 antigen.
Commonest cause of death related to AS is renal failure secondary to amyloidosis in AS.
Colchicine
Colchicine – inhibits Leukocyte Migration and Phagocytosis by blocking Tubulin Polymerization. The side effects are Nausea and Diarrhea, should not be used in Renal Insufficiency. It is important to remember that colchicine has no role in acute gout. Acute gout managed by NSAIDs and Steroids.
Fibromyalgia syndrome
Fibromyalgia syndrome is the most common cause of chronic pain in adults. Female to male ratio is 4:1. Diagnosis requires that spontaneous pain be present for over 3 months duration along the spine and in all four quadrants of the body, and pain must be elicited at 11 out of 18 "tender points" on digital palpation.
Iloprost
5 day intravenous infusion Of Iloprost has been proved effective in the treatment of severe Raunaud's secondary to Scleroderma. It is also of proven efficacy in Heparin induced thrombocytopenia, Macular degeneration, Angina pectoris. However it is not FDA approved for these purposes.
FDA has approved its use only in pulmonary arterial hypertension
FDA has approved its use only in pulmonary arterial hypertension
Quiz
This is a picture of a 35 year old male who presented with hematuria and hypertension. What is the diagnosis?
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Wegener's Granulomatosis: It is a systemic vasculitis with characteristic involvement of upper airway, lower airway and kidneys. (Another question on the USMLE may test the fact that blood test for cANCA is positive in Wegener's Granulomatosis.)
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Wegener's Granulomatosis: It is a systemic vasculitis with characteristic involvement of upper airway, lower airway and kidneys. (Another question on the USMLE may test the fact that blood test for cANCA is positive in Wegener's Granulomatosis.)
Gout and Pseudogout crystals
Rhomboid positively birefringent crystals = CPPD i.e. pseudogout ..... think is it hemochromatosis? (in contrast to needle shaped and negative birefringent Uric acid crystals)
Reiter's Syndrome
Reiter's Syndrome is a triad of Urethritis, Conjunctivitis and Arthritis (which is non infectious but often follows infections, is associated with HLA-B27 and is usually polyarticular)
American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus (SLE)
There are a total of 11 criteria, 4 of which if documented at any time during the patient's history make the diagnosis of SLE very likely (specificity = 95% and sensitivity = 75%). I like to remember them as
4 skin related criteria,
4 systemic criteria and
3 lab criteria.
Skin related criteria:
1) Malar rash: Fixed erythema, flat or raised, over the malar regions
2) Discoid rash: Erythematous circular raised patches with adherent keratotic scaling and follicular plugging; with or without atrophic scarring
3) Photosensitivity: Exposure to ultraviolet light (sun) causes rash
4) Oral ulcers: Includes oral and nasopharyngeal ulcers, observed by physician
Systemic criteria:
5) Arthritis: Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion
6) Serositis: Pleuritis or pericarditis documented by EKG changes, pericardial rub or evidence of effusion
7) Renal disorder: Proteinuria >0.5 g/d or 3+, or cellular casts
8) Neurologic disorder: Seizures or psychosis without known etiology
Lab Criteria:
9) Hematologic disorder: Hemolytic anemia or leukopenia (<4000/L) or lymphopenia (<1500/L) or thrombocytopenia (<100,000/L) in the absence of offending drugs
10) Immunologic disorder: Anti-dsDNA, anti-Sm, and/or anti-phospholipid
11) Antinuclear antibodies: An abnormal titer of ANA by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to induce ANAs
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