Download - WHO Classification of Lupus Nephritis
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WHO Classification of Lupus NephritisCLASS I Minimal Mesangial Glomerulonephritis
- histologically normal on light microscopy but with mesangial deposits on electron microscopy
CLASS II Mesangial Proliferative Lupus Nephritis- typically responds completely to treatment with corticosteroids
CLASS III Focal Proliferative Nephritis- often successfully responds to treatment with high doses of corticosteroids
CLASS IV Diffuse Proliferative Nephritis- mainly treated with corticosteroids and immunosuppressant drugs
CLASS V Membranous Nephritis- characterized by extreme edema and protein loss
CLASS VI Glomerulosclerosis
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International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus
NephritisCLASS I Minimal Mesangial Lupus Nephritis
- normal glomeruli by LM but mesangial immune deposits by IFCLASS II Mesangial Proliferative Lupus Nephritis
- purely mesangial hypercellularity of any degree or mesangial matrix expansion by LM, with mesangial immune deposits- may be a few isolated subepithelial or subendothelial deposits visible by IF or EM, but not by LM
CLASS III Focal Lupus Nephritis- active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations
III-(A) Active lesions: focal proliferative lupus nephritisIII-(A/C) Active and chronic lesions: focal proliferative and sclerosing lupus nephritisIII-(C) Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis
(LM – Light Microscopy, IF – Immunofluorescence Microscopy, EM – Electron Microscopy)
Weening et. al. 2004. The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:241-250.
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International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus
NephritisCLASS IV Diffuse Lupus Nephritis
- active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis involving 50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations- this class is divided into:
1. diffuse segmental(IV-S) lupus nephritis when 50% of the involved glomeruli have segmental lesions
2. diffuse global (IV-G) lupus nephritis when 50% of the involved glomeruli have global lesions
- segmental is defined as a glomerular lesion that involves less than half of the glomerular tuft- this class includes cases with diffuse wire loop deposits but with little or no glomerular proliferation
IV-S (A) Active lesions: diffuse segmental proliferative lupus nephritisIV-G (A) Active lesions: diffuse global proliferative lupus nephritisIV-S (A/C) Active and chronic lesions: diffuse segmental proliferative and sclerosing lupus nephritis Active and chronic lesions: diffuse global proliferative and sclerosing lupus nephritisIV-S (C) Chronic inactive lesions with scars: diffuse segmental sclerosing lupus nephritisIV-G (C) Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis
Weening et. al. 2004. The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:241-250.
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International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus
NephritisCLASS V Membranous Lupus Nephritis
- global or segmental subepithelial immune deposits or their morphologic sequelae by LM and by IF or EM, with or without mesangial alterations- may occur in combination with class III or IV in which case both will be diagnosed- shows advanced sclerosis
CLASS VI Advanced Sclerosing Lupus Nephritis- 90% of glomeruli globally sclerosed without residual activity
(LM – Light Microscopy, IF – Immunofluorescence Microscopy, EM – Electron Microscopy)
Weening et. al. 2004. The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:241-250.
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3. Enumerate the side-effects of cyclophosphamide
• Side effects of Cyclophosphamide– diarrhea– lethargy– chemotherapy-induced nausea and vomiting– bone marrow suppression– darkening of the skin/nails– alopecia (hair loss) or thinning of hair– changes in color and texture of the hair– hemorrhagic cystitis
Reference: http://www.drugs.com/sfx/cyclophosphamide-side-effects.html
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3. Enumerate the side-effects of cyclophosphamide
• Side effects of Cyclophosphamide – carcinogenic, potentially causing transitional cell
carcinoma of the bladder as a long-term complication
– lower the body's immune system – cause temporary or (rarely) permanent sterility.
Reference: http://www.drugs.com/sfx/cyclophosphamide-side-effects.html
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Some side effects with cyclophosphamide are potentially serious and should be reported immediately to a healthcare
provider. These include but are not limited to:
• Signs of an infection, such as chills or a fever • Blood in the stool • Blood in the urine (which can be a sign of bladder damage) • Severe mouth sores • Signs of an allergic reaction, including unexplained rash, hives,
itching, and unexplained swelling. • Severe nausea, vomiting, or diarrhea • Decreased urination, which may be a sign of kidney damage • Difficulty breathing or water retention, which may be signs of
congestive heart failure • Any unusual moles, skin sores that do not heal, or unusual lumps
(which can be signs of new tumors or cancers)
Reference: http://www.drugs.com/sfx/cyclophosphamide-side-effects.html
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Clinical and radiographic manifestations of musculoskeletal TB
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TB of Bones and Joints
• Weight-bearing joints– spine 40%– hips 13%– knees 10%ff
• Phemister’s Triad– Juxta-articular osteoporosis– Peripherally located osseous erosions– Gradual narrowing of the intra-osseous space
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA
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Pott’s Disease (Tuberculous Spondylitis)• most dangerous form of musculoskeletal TB– bone destruction, deformity, and paraplegia
• Progressive bone destruction, >2 adjacent vertebral bodies– leads to vertebral collapse and kyphosis (due to
collapse in anterior spine)• Spinal canal narrowing: abscesses, granulation
tissue or direct dural invasion– leading to SC compression and neurologic deficits
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA
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Clinical Manifestations
• Back pain, stiffness– thoracic and lumbosacral region most common
• Constitutional symptoms = fever, weight loss• Most deadly complication = paraplegia– due to abscess compressing the spinal cord
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA
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Radiographic Findings
• Lytic destruction of anterior portion of vertebral body• Increased anterior
wedging• Collapse of vertebral
body
Reference: Emedicine. 2009. Pott’s Disease. Retrieved February 16, 2010 from http://emedicine.medscape.com/article/226141-overview
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CT Scan– provides better bony detail of irregular lytic
lesions, sclerosis, disk collapse and disruption of bone circumference
– reveals early lesions and is more effective for defining the shape and calcification of soft-tissue abscesses.
Reference: Emedicine. 2009. Pott’s Disease. Retrieved February 16, 2010 from http://emedicine.medscape.com/article/226141-overview
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Radiographic Manifestation
CT scan demonstrating destruction of the right pedicle of T10 due to Pott's disease
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA
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Tuberculosis of Hip and Knee Joints• Unrecognized joint destruction• Hip joints– Involves the head of the femur (common)– Painful
• Knee joints– Pain and swelling
• Diagnosis: biopsy, tissue culture and synovial fluid exam (thick in appearance, high protein concentration and variable cell count)
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo. 2008. Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA
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Tuberculosis of the Hip
Lesion on femoral head and acetabulumKissing Lesion: hallmark of TB infection
Reference: Singh, Arun Pal. 2009. X-Ray of TB of Hip Joint. Retrieved February 16, 2010 fromhttp://boneandspine.com/muculoskeletal-radiology/xray-of-tuberculosis-of-hip-joint/
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calcified debris in the supra-patellar bursa
Reference: Palmer & Reeder. 2009. The Imaging of Tropical Diseases. Retrieved February 16, 2010 from http://www.isradiology.org/tropical_deseases/tmcr/chapter5/lymphadenopathy.htm
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Clinical, laboratory, radiographic manifestations of genitourinary TB
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Clinical Manifestations
• Local symptoms predominate• Up to one third of patients may concomitantly
have pulmonary manifestations• Common symptoms include: – Urinary frequency– Dysuria– Nocturia– Hematuria– Abdominal and Flank pain
Harrison’s Principle of Internal Medicine, 17th ed. P1011-1012
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Clinical Manifestations
• In females:– May affect the fallopian tubes and the
endometrium causing infertility, pelvic pain and menstrual abnormalities
• In males:– Primarily affects the epididymis, producing a slight
tender mass that may drain externally through a fistulous tract; orchitis and prostatitis.
Harrison’s Principle of Internal Medicine, 17th ed. P1011-1012
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Laboratory Manifestations
• Urinalysis:– Pyuria and Hematuria
• Urine Culture:– Pyuria but negative for common organisms
causing UTI– Culture of three morning urine specimens positive
for Mycobacterium tuberculosis is a definitive diagnosis.
Harrison’s Principle of Internal Medicine, 17th ed. P1011-1012
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Radiographic Manifestations
• Intravenous pyelography• Abdominal CT• MRI
Deformities, obstructions, calcifications and ureteral strictures are suggestive findings in genitourinary tuberculosis.
Harrison’s Principle of Internal Medicine, 17th ed. P1011-1012
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Side effects of anti-TB medications HREZ
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Isoniazid• Isoniazid-induced hepatitis-most common major
toxic effect• Peripheral neuropathy• CNS toxicity-memory loss, psychosis,seizures• Fever and skin rashes• Drug-induced SLE• Hematologic abnormalities• Provocation of pyridoxine deficiency anemia• Tinnitus• Gastrointestinal discomfort
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 773
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Rifampicin
• Orange urine, sweat and tears• Rashes• Thrombocytopenia• Nephritis• Light-chain proteinuria• Flu-like sydrome(fever, chills, myalgia, anemia
and thrombocytopenia)
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 774
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Ethambutol
• Retrobulbar neuritismost common serious adverse eventLoss of visual acuity and red-green color blindness
• Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis)
• Fever and lymphadenopathy
http://www.drugs.com/sfx/ethambutol-side-effects.html
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 774
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Pyrazinamide
• Hepatotoxicity-major adverse effect• Nausea• Vomiting• Fever• hyperuricemia
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 775
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Anti-TB regimen in special situations of liver disease, renal impairment, and pregnancy.
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Liver disease• Patients with pre-existing liver disease can receive the usual TB
regimens provided that there is no clinical evidence of chronic liver disease, hepatitis virus carriage, a past history of acute hepatitis, current excessive alcohol consumption.
• However, hepatotoxic reactions to anti-TB drugs may be more common among these patients and should therefore be anticipated
• The first-line drugs HRZ are all associated with hepatotoxicity.– Pyrazinamide is the most hepatotoxic
Treatment of tuberculosis: guidelines - 4th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf
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• The more unstable or severe the liver disease is, the fewer hepatotoxic drugs should be used.
• In general, patients with chronic liver disease should not receive pyrazinamide. All other drugs can be used, but close monitoring of liver enzymes is advised.
If the serum AST level is more than 3 times normal before the initiation of treatment, the following regimens should be considered .
• Two hepatotoxic drugs (rather than the three in the standard regimen): 9 months of HRE2 months of HRSE followed by 6 months of HR6–9 months of RZE.
• One hepatotoxic drug: 2 months of HES, followed by 10 months of HE
• No hepatotoxic drugs: 18–24 months of streptomycin, ethambutol and a fluoroquinolone.
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Renal impairment• The recommended initial TB treatment regimen for patients with
renal failure or severe renal insufficiency is 2 months of HRZE, followed by 4 months of HR.
• Isoniazid and rifampicin are eliminated by biliary excretion, so no change in dosing is necessary.
• There is significant renal excretion of ethambutol and metabolites of pyrazinamide and doses should therefore be adjusted.
• Three times per week administration of these two drugs at the following doses is recommended: pyrazinamide (25 mg/kg), and ethambutol (15 mg/kg)
Treatment of tuberculosis: guidelines - 4th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf
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Renal impairment• While receiving isoniazid, patients with severe renal insufficiency or
failure should also be given pyridoxine in order to prevent peripheral neuropathy.
• Streptomycin should be avoided in patients with renal failure because of an increased risk of nephrotoxicity and ototoxicity.
• If streptomycin must be used, the dosage is 15 mg/kg, two or three times per week, to a maximum of 1 gram per dose, and serum levels of the drug should be monitored.
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Pregnancy• Women of childbearing age should be asked about current or
planned pregnancy before starting TB treatment. • A pregnant woman should be advised that successful treatment of
TB with the standard regimen is important for successful outcome of pregnancy.
• With the exception of streptomycin, the first line anti-TB drugs are safe for use in pregnancy– streptomycin is ototoxic to the fetus and should not be used during
pregnancy. • Pyridoxine supplementation is recommended for all pregnant
women taking isoniazid
Treatment of tuberculosis: guidelines - 4th ed. WHO http://whqlibdoc.who.int/publications/2010/9789241547833_eng.pdf