1. RARE CASE SCENARIO Name: Mrs A, Age: 34years, Sex: female,
Occupation: house maker
Marital status: married

2. Presenting complaints: Family history:
Generalised swelling of body since fifteen days duration, Fever, myalgia, multiple joint pain, Rash over extremities (L>U) for fifteen days duration
Cough with expectoration since five days,
SOB since five days.
Decreased urine output since three days.
Family history:
No history any renal disease in family
Personal history:
Irregular mensural cycles,
Mixed diet, bowel movements regular
No substance abuse
Past history:
Hypothyroidism since one year on Thyronorm 50 ug/day.
No Diabetes mellitus, Hypertension or
Bronchial Asthma or Tuberculosis

3. Examination: Pulse rate : 100/min, Blood Pressure: 152/100 mmhg,
Respiratory rate: 20/min
Temperature normal
pallor present, anasarca present.
Palpable rash present on extremities (L>U).
No lymphadenopathy.
Wt-50kg, Ht-159cm, BSA-1.5m2, BMI-19.8.
Systemic examination:
RS: Breath sounds decreased bilaterally (R>L)
CVS: Tachycardia,
P/A: ascites present, no organomegaly.
CNS: HMF normal, no focal deficits.

4. Blood biochemistry
BLOOD UREA NITROGEN
60mg/dl
SERUM CREATININE
2.3mg/dl
SODIUM/POTASSIUM/CHLORIDE
136/4.2/98meq/ml
BILIRUBIN
1.2mg/dl
SGOT/SGPT
40/33
ALP
142iu/ml
TSP/ALBUMIN
5.2/2.8 mg/dl
TOTAL CHOLESTEROL
145mg/dl
LDL
95mg/dl
TRIGLYCERIDES
156mg/dl
CALCIUM/MAGNESIUM/UA/PHOSPHRUS
8.5/1.2/6/3.3 mg/dl
FBS/PPBS
92/141mg/dl
Iron/%saturation/TIBC/ferritin
102/45/255/158
PT/aPTT
12.2/30.2
CRP
4mg/dl
PROCACITONIN
4.5
T3/T4/TSH
1.1/8.2/25.3
LDH
401
24HOUR TV/TP
900ML/0.72grams/day C3
13mg/dl C4
2mg/dl
Pleural fluid analysis
transudative

5. pathology
Hb%
7.2gm%
PCV
25.3
TLC
9200 PC
1.2
PERIPHERAL SMAER
Macrocytic and microcytic anaemia, no schistocytes, no parasites
ESR
49ml/2hr
CUE-pH 7 SG
1.010
PROTEIN 2+
SUGAR
Nil EC
2-3
RBCs
8-10
WBCs
3-5

6. Imaging studies Chest X-ray
Bilateral pleural effusion(R>>L) with underlying lung consolidation
HRCT Thorax
Bilateral moderate to severe pleural effusion(R>>>L) with underlying lung consolidation with scattered lung infiltrates, mediastinum was normal
USG abdomen and pelvis
Gross ascites, no organomegaly, both kidneys are normal in size with raised echotexture and maintained CMD, Pelvic organs are normal.
2D-ECHO
EF-55%, NO RWMA, grade 1 DD+, RSVP- 25mmhg

7. Microbiological investigations
Urine culture
No growth
Blood culture(1set)
Sputum culture
TB screening
negative
Mountau text
<5mm after 72 hours
Immunology/serology
Hbsag ( ELFA)
neg
Anti HCV Ab (ELISA)
HIV(ELISA) NR
ANA(IF)
3+ (speckled, 1:100)
DsDNA
c&p ANCA
ASO titre
Neg(<200)
Rheumatoid factor
161IU/ml POSITIVE(>20IU/ml)

8. Provisional diagnosis
Rapidly progressive renal failure
Hypertension
Hypothyroidism
Mixed anaemia
LRTI

9. Initial management Diuretics Antibiotics Two unit blood transfusion
Other supportive measures
IVMP 1gm pulses for three days.

10. Renal biopsy(8365/18)

11. Special investigations
Serum IgG
875mg/dl
Serum IgE
480mg/dl
Serum IgA
179mg/dl
Serum free light assay
Kappa-8mg/dl, lamda-15mg/dl. ( ratio <2)
Urine BJPs
absent
Serum electrophoresis
Negative for M band
Urine electrophoresis
Normal pattern
DCT/ICT
NEGATIVE
BONE MARROW EXAMINATION
NORMAL

12. SERUM CRYOGLOBULINS

13. SKIN BIOPSY(8465/18) C3
IgG

14. FINAL DIAGNOSIS CRYOGLOBULINEMIC GLOMERLUNEPHRITIS
WITH SKIN INVOLVEMENT
IDIOPATHIC (ESSENTIAL) MIXED CRYOGLOBULINEMIA
HYPERTENSION
HYPOTHYROIDISM
ANAEMIA OF CHRONIC INFLAMMATION

15. MANAGEMENT Antihypertensives( tab cilnidipine 10mg OD) Diuretics
IVMP 1gm for three days and iv cyclophosphamide 1gms ( NIH protocol). Followed 0.5mg/kg oral prednisolone.
Other supportive treatment.
KDIGO Recommendations: Among MPGN patients with nephrotic-range proteinuria and/or rapid loss of kidney function and an acute flare of cryoglobulinemia, one of the following therapies should be considered: Plasma exchange (3 liters of plasma thrice weekly for two to three weeks) Rituximab (375 mg/m2 per week for four weeks); OR Cyclophosphamide (2 mg/kg per day for two to four months) Plus Methylprednisolone pulses (0.5 to 1 g/day for three days).

16. Patient follow-up after month
Complaints- SOB on exertion,
BP-140/70mmhg
Weight-45kg
No anasarca, pallor present, resolving rash.
Systemic examination is normal.
Received 2nd dose cyclophosphamide 1gm on 10/10/2018
Hb%
TLC
PLATELET
BUN
SCR
24HR TP
TSH
CUE-PRO
RBCs
Pus cells
7gm%
6200
1.5 36 1
0.45gm/day
3.5 1+
nil
1-2

17. Discussion
Cryoglobulins are immunoglobulins in serum that precipitate at temperature below 37⁰C and re-dissolve on rewarming.

21. SUMMARY AND CONCLUSION
Cryoglobulinemia is a rare clinical entity.
Renal involvement varies from 8-58% of cases
Awareness of its clinical spectrum is important, because diagnosis is facilitated by the demonstration of cryoglobulins in the serum.
Treatment is challenging, given the end-organ damage and frequent relapses.
Uniform management guidelines are difficult because of heterogeneity.