بسم  الله  الرحمن الرحيم

Total Body Necrosis

In late 2004, a 23 year old woman who complained of polyarthralgia, mouth ulcers, and alopecia, was admitted to another hospital where she was diagnosed SLE And class IV nehritis. (ANA) & (ds ANA) were positive..

At that time renal function was normal, liver function was normal except that albumin was low (12gm/L)

Pt. was treated with methyl prednisolne Pt. was treated with methyl prednisolne (1g IV) for three days followed by oral (1g IV) for three days followed by oral prednisolone (60mg) in a tapering dose. prednisolone (60mg) in a tapering dose.

The total duration of treatment was unknown. The total duration of treatment was unknown. Since 2004, the woman had frequent relapses Since 2004, the woman had frequent relapses of disease activity. of disease activity. She was treated as described above with pulse She was treated as described above with pulse steroid followed by a tapering Dose of steroid followed by a tapering Dose of prednisolone. prednisolone.

In march 2006, the woman was admitted In march 2006, the woman was admitted to KAUH with dyspnea, lower – limb edema, decreased urine output, and polyarthragia.

On Clinical Examination The following values were recorded: The following values were recorded: Temperature (37.1 o C) Temperature (37.1 o C) Blood pressure (149/90mmHg) Blood pressure (149/90mmHg) Heart rate (84 beats/min) Heart rate (84 beats/min) elevated jugular venous pressure (JVP) elevated jugular venous pressure (JVP) Body weight (90kg) and lower limb edema. Body weight (90kg) and lower limb edema. The chest examination bilateral basal The chest examination bilateral basal crepitation. The remainder of the exam was crepitation. The remainder of the exam was unremarkable. unremarkable.

LAB DATA Creatinine 402 mmo/L Creatinine 402 mmo/L Po4 3.3 mmol/L Po4 3.3 mmol/L Calcium 2.4 mmol/L Calcium 2.4 mmol/L Alkaline phospatase 36 I.U./L Alkaline phospatase 36 I.U./L Albumin 19 g Albumin 19 g Repeat renal biopsy : diffuse proliferative GN with crescent (class lV) Repeat renal biopsy : diffuse proliferative GN with crescent (class lV)

She was treated with: She was treated with: Pulse methyl prednisolone 1gm i.v.for 3 days Pulse methyl prednisolone 1gm i.v.for 3 days Then oral prednisolone 60 mg to be tapered Then oral prednisolone 60 mg to be tapered after 1 month after 1 month Mycophenolate mofetil Mycophenolate mofetil H.D. H.D. Phosphate binders Phosphate binders

The Patient Responded Began to produce urine in the range of Began to produce urine in the range of litter/day. The CaPO4 homeostasis was litter/day. The CaPO4 homeostasis was well- maintained and she came out of dialysis for 1/12 almost symptom free and well- maintained and she came out of dialysis for 1/12 almost symptom free and with no pulmonary edema or lower – limb with no pulmonary edema or lower – limb edema. edema.

On 1 st April 2008, On 1 st April 2008, the woman was discharged with creatinine (330mmol/L) the woman was discharged with creatinine (330mmol/L) and PO4 1.4mmo1/L to be assessed once each week. and PO4 1.4mmo1/L to be assessed once each week. On 2 July 2006, On 2 July 2006, she was admitted to KAUH with skin lesions that started at the she was admitted to KAUH with skin lesions that started at the glutei region. glutei region. The lesions were diagnosed at the other The lesions were diagnosed at the other hospital as glutei abscises. hospital as glutei abscises.

The lesions were drained at the other hospital therefore, the precise characteristics of the lesions were not clear. On re-admission to our hospital, the lesions typically were violaceous, painful, plaque-like, and involved in the dermis and subcutaneous fat on back, buttocks, thighs, and breast. Subsequently the lesions progressed to ischemic/necrotic ulcers. The patient denied a history of fever or trauma.

On Clinical Examination The following values were recoded The following values were recoded body temperature (37 o C) body temperature (37 o C) Blood pressure (140/80mmHg) jugular Blood pressure (140/80mmHg) jugular venous pressure was not elevated and venous pressure was not elevated and there was no lower limb edema. there was no lower limb edema.

Laboratory Tests Showed creatinine 763mmol Showed creatinine 763mmol Alkaine phosphatase 149IU/L Alkaine phosphatase 149IU/L Calcium 1.66 mmo1/L Calcium 1.66 mmo1/L Phosphate 4.24mmo1/L Phosphate 4.24mmo1/L Calcium phosphate 7.0 mmo1/L Calcium phosphate 7.0 mmo1/L Parathyroid hormone 38 Parathyroid hormone 38 ANA 1:320 g/L ANA 1:320 g/L dsDNA 52iu/ml C3 0.87g/l, C4 0.33g/L dsDNA 52iu/ml C3 0.87g/l, C4 0.33g/L CRP 130mg/L CRP 130mg/L Normal protein C, protein S,anticardiolipin and cryglobinemia. Normal protein C, protein S,anticardiolipin and cryglobinemia.

DIAGNOSIS ?

Differential Diagnosis Cholesterol Embolization. Cholesterol Embolization. Warfarin Necrosis. Warfarin Necrosis. Cryoglobulinemia Cryoglobulinemia Vasulitis Vasulitis Nephrogenic Systemic Fibrosis Nephrogenic Systemic Fibrosis Hyperoxaluria Hyperoxaluria

Histology Examination Revealed that dermis and epidermis Revealed that dermis and epidermis show necrosis and fibrosis. show necrosis and fibrosis. Epidermis, subcutaneous fat and blood Epidermis, subcutaneous fat and blood vessels with marked calcification vessels with marked calcification

calciphylaxis

The patient was treated with daily The patient was treated with daily dialysis dialysis And oral prednisolone (0.5mt/1kg/1day And oral prednisolone (0.5mt/1kg/1day And phospate binder And phospate binder o Pain killers (opiates) o Wound care o Antibiotics o Vitamin K+ Albumin

After all treatment patient transfer to ICU with septic shock. After all treatment patient transfer to ICU with septic shock. Repeated PTH was 5.3, Ca 2.2mmol/l Repeated PTH was 5.3, Ca 2.2mmol/l PO4 1.4mmol/l PO4 1.4mmol/l She patient died due to sepsis. She patient died due to sepsis.

Calciphylaxis Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis and thrombosis. Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis and thrombosis.

Risk Factors for the Developmennt Calciphylaxis The role of Obesity. The role of Obesity. Ca, Po4 and Ca x Po4 product. Ca, Po4 and Ca x Po4 product. The role of warfarin. The role of warfarin. The role protein C and/or Protein S The role protein C and/or Protein S Deficiency. Deficiency. Fetuin – A Glycoprotein and Matrix gla Fetuin – A Glycoprotein and Matrix gla protein. protein.

The role of protein malnutrition. The role of protein malnutrition. The role of PTH. The role of PTH. The role of Vitamin D Analogs. The role of Vitamin D Analogs.

The Diagnosis of Calciphylaxis Physical Examination. Physical Examination. Exclusion of other Vascular Disease. Exclusion of other Vascular Disease. Tissue Biopsy. Tissue Biopsy. Measurements of Transcutaneous Measurements of Transcutaneous oxygen saturation. oxygen saturation. Bone Scans. Bone Scans. Xeroradiography. Xeroradiography.

MANAGEMENT AND PREVENTION

An aggressive program of wound care An aggressive program of wound care and adequate pain control. and adequate pain control. Avoidance of local tissue trauma, Avoidance of local tissue trauma, including subcutaneous injections. including subcutaneous injections. Among dialysis patients, normalize Among dialysis patients, normalize serum PTH levels (intact PTH should serum PTH levels (intact PTH should be between 150 to 300 pg/ml) be between 150 to 300 pg/ml) Parathyroidectomy. Parathyroidectomy.

SUMMARY SUMMARY Preventive Strategies Preventive Strategies Reassess the Dialysis Prescription. Reassess the Dialysis Prescription. Improve serum calcium and Improve serum calcium and phosphorus levels phosphorus levels Reassess the use of warfarin. Reassess the use of warfarin. Consider Parathyroidectomy. Consider Parathyroidectomy.

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