الالاللهاللهبسمبسمالرحالرحرحمنرحمن

يميم

Total Body Total Body NecrosisNecrosis

In late 2004, a 23 year old woman In late 2004, a 23 year old woman whowho

complained of polyarthralgia, mouth complained of polyarthralgia, mouth ulcers, ulcers,

and alopecia, was admitted to and alopecia, was admitted to another another

hospital where she was diagnosed hospital where she was diagnosed SLE SLE

And class IV nehritis.And class IV nehritis.

(ANA) & (ds ANA) were positive.(ANA) & (ds ANA) were positive.

..

At that time renal At that time renal function function

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

Pt. was treated with methyl Pt. was treated with methyl prednisolne prednisolne

(1g IV) for three days followed by (1g IV) for three days followed by oral oral

prednisolone (60mg) in a tapering prednisolone (60mg) in a tapering dose. dose.

The total duration of treatment was The total duration of treatment was unknown.unknown.

Since 2004, the woman had frequent Since 2004, the woman had frequent relapsesrelapses

of disease activity. of disease activity. She was treated as described above with She was treated as described above with

pulse pulse steroid followed by a tapering Dose of steroid followed by a tapering Dose of prednisolone.prednisolone.

In march 2006, the woman was In march 2006, the woman was admitted admitted

to KAUH with dyspnea, lower – limb to KAUH with dyspnea, lower – limb edema,edema,

decreased urine output, and decreased urine output, and polyarthragia.polyarthragia.

On Clinical On Clinical ExaminationExamination The following values were The following values were

recorded:recorded: Temperature (37.1Temperature (37.1ooC)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 Body weight (90kg) and lower limb

edema. edema. The chest examination bilateral basal The chest examination bilateral basal crepitation . The remainder of the crepitation . The remainder of the

exam was exam was unremarkable.unremarkable.

LAB DATALAB 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./LAlkaline phospatase 36 I.U./L

Albumin 19 g Albumin 19 g

Repeat renal biopsy : diffuse proliferative GN Repeat renal biopsy : diffuse proliferative GN with crescent (class lV)with crescent (class lV)

She was treated with:She was treated with: Pulse methyl prednisolone 1gm Pulse methyl prednisolone 1gm

i.v.for 3 daysi.v.for 3 days Then oral prednisolone 60 mg to Then oral prednisolone 60 mg to

be taperedbe tapered

after 1 monthafter 1 month Mycophenolate mofetil Mycophenolate mofetil H.D.H.D. Phosphate bindersPhosphate binders

The Patient RespondedThe Patient Responded

Began to produce urine in the range of Began to produce urine in the range of 1.5-21.5-2

litter/day. The CaPO4 homeostasis was litter/day. The CaPO4 homeostasis was

well- maintained and she came out of well- maintained and she came out of dialysis for 1/12 almost dialysis for 1/12 almost symptom free and symptom free and

with no pulmonary edema or lower – with no pulmonary edema or lower – limb limb

edema.edema.

On 1On 1stst April 2008, April 2008, the woman was discharged with creatinine the woman was discharged with creatinine

(330mmol/L) (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 she was admitted to KAUH with skin lesions that

started at the 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 The lesions were drained at the other

hospital therefore, the precise characteristics hospital therefore, the precise characteristics

of the lesions were not clear. On re-admission of the lesions were not clear. On re-admission

to our hospital, the lesions typically were to our hospital, the lesions typically were

violaceous, painful, plaque-like, and involved violaceous, painful, plaque-like, and involved

in the dermis and subcutaneous fat on back, in the dermis and subcutaneous fat on back,

buttocks, thighs, and breast. Subsequently the buttocks, thighs, and breast. Subsequently the

lesions progressed to ischemic/necrotic ulcers.lesions progressed to ischemic/necrotic ulcers.

The patient denied a history of fever or trauma. The patient denied a history of fever or trauma.

On Clinical On Clinical ExaminationExamination

The following values were The following values were recoded recoded

body temperature (37body temperature (37ooC) C) Blood pressure (140/80mmHg) Blood pressure (140/80mmHg)

jugular jugular

venous pressure was not elevated venous pressure was not elevated and and

there was no lower limb edema.there was no lower limb edema.

Laboratory TestsLaboratory Tests

Showed creatinine 763mmolShowed creatinine 763mmol Alkaine phosphatase 149IU/LAlkaine phosphatase 149IU/L Calcium 1.66 mmo1/LCalcium 1.66 mmo1/L Phosphate 4.24mmo1/LPhosphate 4.24mmo1/L Calcium phosphate 7.0 mmo1/LCalcium phosphate 7.0 mmo1/L Parathyroid hormone 38Parathyroid hormone 38 ANA 1:320 g/LANA 1:320 g/L dsDNA 52iu/ml C3 0.87g/l, C4 0.33g/LdsDNA 52iu/ml C3 0.87g/l, C4 0.33g/L CRP 130mg/L CRP 130mg/L Normal protein C, protein Normal protein C, protein

S,anticardiolipin and cryglobinemia. S,anticardiolipin and cryglobinemia.

DIAGNOSISDIAGNOSIS

??

Differential DiagnosisDifferential Diagnosis

Cholesterol Embolization.Cholesterol Embolization. Warfarin Necrosis.Warfarin Necrosis. CryoglobulinemiaCryoglobulinemia VasulitisVasulitis Nephrogenic Systemic FibrosisNephrogenic Systemic Fibrosis HyperoxaluriaHyperoxaluria

Histology ExaminationHistology Examination

Revealed that dermis and Revealed that dermis and epidermis epidermis

show necrosis and fibrosis.show necrosis and fibrosis.

Epidermis, subcutaneous fat and Epidermis, subcutaneous fat and bloodblood

vessels with marked calcification vessels with marked calcification

calciphylaxcalciphylaxisis

The patient was treated with daily The patient was treated with daily

dialysis dialysis And oral prednisolone And oral prednisolone

(0.5mt/1kg/1day(0.5mt/1kg/1day

And phospate binderAnd phospate bindero Pain killers (opiates)Pain killers (opiates)o Wound careWound careo AntibioticsAntibioticso Vitamin K+ AlbuminVitamin K+ Albumin

After all treatment patient After all treatment patient transfer to ICU with septic shock.transfer to ICU with septic shock.

Repeated PTH was 5.3, Ca Repeated PTH was 5.3, Ca 2.2mmol/l2.2mmol/l

PO4 1.4mmol/lPO4 1.4mmol/l She patient died due to sepsis.She patient died due to sepsis.

CalciphylaxisCalciphylaxis

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

Risk Factors for the Risk Factors for the Developmennt Developmennt CalciphylaxisCalciphylaxis

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 Fetuin – A Glycoprotein and Matrix

glagla 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 The Diagnosis of CalciphylaxisCalciphylaxis

Physical Examination.Physical Examination. Exclusion of other Vascular Exclusion of other Vascular

Disease.Disease. Tissue Biopsy.Tissue Biopsy. Measurements of Transcutaneous Measurements of Transcutaneous

oxygen saturation.oxygen saturation. Bone Scans.Bone Scans. Xeroradiography.Xeroradiography.

MANAGEMENT MANAGEMENT

ANDAND PREVENTIONPREVENTION

An aggressive program of wound An aggressive program of wound carecare

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 shouldserum PTH levels (intact PTH should

be between 150 to 300 pg/ml)be between 150 to 300 pg/ml) Parathyroidectomy.Parathyroidectomy.

SUMMARYSUMMARY Preventive StrategiesPreventive Strategies Reassess the Dialysis Reassess the Dialysis

Prescription.Prescription. Improve serum calcium and Improve serum calcium and

phosphorus levelsphosphorus levels Reassess the use of warfarin.Reassess the use of warfarin. Consider Parathyroidectomy.Consider Parathyroidectomy.

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