1. WHO Classification of Lupus Nephritis
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

2. International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus Nephritis
CLASS I
Minimal Mesangial Lupus Nephritis
- normal glomeruli by LM but mesangial immune deposits by IF
CLASS 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 nephritis
III-(A/C) Active and chronic lesions: focal proliferative and sclerosing lupus
nephritis
III-(C) Chronic inactive lesions with glomerular scars: focal sclerosing lupus
(LM – Light Microscopy, IF – Immunofluorescence Microscopy, EM – Electron Microscopy)
Weening et. al The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:

3. International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus Nephritis
CLASS 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:
diffuse segmental(IV-S) lupus nephritis when 50% of the involved glomeruli have segmental lesions
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 nephritis
IV-G (A) Active lesions: diffuse global proliferative lupus nephritis
IV-S (A/C) Active and chronic lesions: diffuse segmental proliferative and sclerosing
lupus nephritis
Active and chronic lesions: diffuse global proliferative and sclerosing lupus
nephritis
IV-S (C) Chronic inactive lesions with scars: diffuse segmental sclerosing lupus
IV-G (C) Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis
Weening et. al The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:

4. International Society of Nephrology/Renal Pathology Society (INR/RPS) 2003 Classification of Lupus Nephritis
CLASS 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 The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. J Am Soc Nephrol 15:

5. 3. Enumerate the 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
Hemorrhagic cystitis is a frequent complication, but this is prevented by adequate fluid intake and Mesna (sodium 2-mercaptoethane sulfonate). Mesna is a sulfhydryl donor and binds acrolein.
Reference:

6. 3. Enumerate the 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:

7. Signs of an infection, such as chills or a fever Blood in the stool
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:

8. Clinical and radiographic manifestations of musculoskeletal TB

9. TB of Bones and Joints Weight-bearing joints Phemister’s Triad
spine 40%
hips 13%
knees 10%ff
Phemister’s Triad
Juxta-articular osteoporosis
Peripherally located osseous erosions
Gradual narrowing of the intra-osseous space
In the United States, tuberculosis of the bones and joints is responsible for ~10% of extrapulmonary cases. In bone and joint disease, pathogenesis is related to reactivation of hematogenous foci or to spread from adjacent paravertebral lymph nodes.
While the upper thoracic spine is the most common site of spinal tuberculosis in children, the lower thoracic and upper lumbar vertebrae are usually affected in adults.
Reference: Fauci. Braunwald. Kasper. Hauser. Longo. Jameson. Loscalzo Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

10. 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 Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

11. 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 Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

12. Radiographic Findings
Lytic destruction of anterior portion of vertebral body
Increased anterior wedging
Collapse of vertebral body
Reference: Emedicine Pott’s Disease. Retrieved February 16, 2010 from

13. 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 Pott’s Disease. Retrieved February 16, 2010 from

14. 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 Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

15. 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 Harrison’s Principles of Internal Medicine, 17th Edition. McGraw-Hill. USA

16. Tuberculosis of the Hip
femoral head has disappeared, the acetabulum is irregular and sclerotic, and there are cystic changes both in the femoral neck and around the joint.
Lesion on femoral head and acetabulum
Kissing Lesion: hallmark of TB infection
Reference: Singh, Arun Pal X-Ray of TB of Hip Joint. Retrieved February 16, 2010 from

17. calcified debris in the supra-patellar bursa
A healed but badly damaged joint, with partial destruction of the upper end of the tibia, and a lot of new bone and loose fragments. There is calcified debris in the supra-patellar bursa.
Reference: Palmer & Reeder The Imaging of Tropical Diseases. Retrieved February 16, 2010 from

18. Clinical, laboratory, radiographic manifestations of genitourinary TB

19. 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. P

20. 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. P

21. 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. P

22. 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. P

23. Side effects of anti-TB medications HREZ

24. 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

25. 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

26. Ethambutol Retrobulbar neuritis
most common serious adverse event
Loss of visual acuity and red-green color blindness
Hypersensitivity syndrome consisting of cutaneous reaction (such as rash or exfoliative dermatitis)
Fever and lymphadenopathy
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 774

27. Pyrazinamide Hepatotoxicity-major adverse effect Nausea Vomiting Fever
hyperuricemia
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 775

28. *Streptomycin Vertigo and hearing loss nausea, vomiting
paresthesia of face
rash
fever
Urticaria
angioneurotic edema
eosinophilia
Katzung, B, Basic and Clinical Pharmacology 10th ed., McGraw Hill 2007, page 775

29. Anti-TB regimen in special situations of liver disease, renal impairment, and pregnancy.

30. 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

31. 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 HRE
2 months of HRSE followed by 6 months of HR
6–9 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.
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.

32. 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

33. 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.

34. 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