Journal of The Association of Physicians of India ■ Vol. 68 ■ July 202068

Cardiorenal AmyloidosisMeenakshi N1, P Soni2, R Anand3, S Bali2, Hari1

1Senior Resident, Family Medicine, 2Senior Consultant, Medicine, 3Senior Consultant, Radiology, Max Superspeciality Hospital, Saket, New DelhiReceived: 08.08.2016; Accepted: 05.08.2019

Abstract Amyloidosis is a conglomeration of diseases due to production and deposition of amyloid, a proteinaceous substance, into organs, tissues, nerves and other places in the body affecting their normal function. This case report is of a 65 year old gentleman, resident of Bihar admitted with a short history of two months. He came with chief complaints of swelling in both lower limbs associated with heaviness in legs, shortness of breath, dizziness, fatigue and passage of frothy urine for two months. He was investigated and found to have proteinuria, low voltage ECG, Echocardiography showed left ventricular hypertrophy, diastolic dysfunction, mitral regurgitation. Cardiac MRI showed dilated cardiomyopathy due to amyloidosis.

and appetite , numbness, t ingling, hypertension, diabetes, tuberculosis, asthma, previous hospitalizations.

On examination the patient was alert , conscious, oriented with no pallor, cyanosis, clubbing, icterus, lymphadenopathy. He was afebrile, pulse 68/min, BP 100/60mmHg, RR 16/min. He had bilateral pitting edema. On auscultation of the chest there were bilateral crepitations; cardiovascular examinat ion sof t S1 and S2 with pansystolic murmur radiating to the axi l la and no thri l l . Per abdomen examination showed parietal edema and no neuro logica l f indings on examination.

T h e p a t i e n t wa s i n ve s t i g a t e d Table 1. Hemogram showed normal leucocyte count (10,000), raised ESR (38). RBS normal (76), LFT showed hypoalbuminemia (OT/PT 52/60,TP 6, Alb 2.2, Glob 3.8, A/G.5/1,), KFT was normal (B. urea 22 , s. creatinine.9).Coagulation and Thyroid profile was normal. Nephrotic range proteinuria (albuminuria-8.514) His Chest X-ray was normal and Ultrasound showed hepatomegaly with Benign prostatic hypertrophy and left kidney cyst. CT abdomen showed mild hepatomegaly with bilateral pleural effusion and diffuse abdominal wall edema.

The patient was further investigated Table 2 which showed hyponatremia and proteinuria. To rule out Multiple myeloma, serum and urine protein e lectrophores is were done which s h o we d n o M s p i k e . K a p p a a n d lambda light chains in serum and urine were sent and were normal. In view of the systolic murmur, ECG and Echocardiography was done. ECG showed low voltage complexes. Echocardiography showed no regional wall motion abnormality of left ventricle. Global LVEF 60%, moderate concentric

Introduction

Amyloidosis (“osis” means increased or an abnormal supply) or “Orphan

disease” is a conglomeration of diseases due to production and deposition of amyloid, an abnormal insoluble low molecular weight protein. Amyloid deposition into organs, tissues, nerves and other places in the body affects the normal function of the area.1 Correct diagnosis is extremely important as each of the af fected system is diseased and each has a different management. Characteristic cross-β-sheet amyloid fibrils accumulate s y s t e m i c a l l y o r a r e l o c a l i z e d t o s p e c i f i c o r g a n s i n a m yl o i d o s i s . 2 There are several different types of amyloid proteins and the three most common systemic Amyloidosis diseases

are AL – A for amyloid and L for Light Chain, AA – A for amyloid, A is for Serum A Protein (also known as SAA) and ATTR – A for amyloid, TTR is for Transthyretin (also known as TTR) protein.3 In this case report we want to highlight a patient with combined cardiac and renal amyloidosis, a rare entity. Case

A 65 year old gentleman, resident of Madhubani district, Bihar was admitted with chief complaints of swelling in both lower limbs gradually increasing for 2 months associated with heaviness in legs . He also had shortness of breath, dizziness, fatigue and passage of frothy urine for the same duration. No history of fever, reduced urine output, hematuria, dysuria, nausea, diarrhoea, constipation, loss of weight

Table 1:

Hemogram Hb 12.3 TLC 10000, (N9,L29.4, M.7,E1.4,B.6), PLT 344000, PCV 38, RBC 3.99, MCV 95.3,MCH 30.9,MCHC 32.4,RDW 13.5

KFT B.urea 17.1 s.creatinine.5 Sodium 126 Potassium 4.9 Chloride 96.5, Bicarbonate 24

LFT T. protein 3.9 Albumin 1.4 Gobulin 2.5, SGOT 53, SGPT 42, GGT 68, ALP 115

SPEP no M spike Free k /ƛ chains in serum

10.6 / 1.2 mg/l

Urine routine Nephrotic range proteinuria (albuminuria-8.514) with no RBC or cast.

Stool R/M and C/s 1-2 pus cells, no growth

Table 2: Hemogram

Hb 12.4PCV 37.1TLC 6.0, Neutrophils 54.8, Lymphocytes 38.4, Monocytes 6.3, Eosinophils.1, Basophils.4Platelet count 197RBC 3.97MCV 93.4MCH 31.3MCHC 33.5RDW 13.1

C A S E R E p o R t S

Journal of The Association of Physicians of India ■ Vol. 68 ■ July 2020 69

Fig. 1: P Lax- Hypertrophied left ventricle with increased myocardial echogenecity (typical speckled appearance of amyloidosis) and left atria enlargement (42 mm)

Fig. 2: P Sax at apical level with hypertrophies left ventricle and increased myocardial echogenecity with speckled appearance

Fig. 3: Tissue Doppler at medial annulus of mitral valve. E’ (tissue Doppler) is reduced –a feature of restrictive physiology

Fig. 5: Short axis MRI image showing diffuse enhancement of left ventricular wall

Fig. 6: 4 chamber gadolinium enhancement

Fig. 7: High power view of the glomerulus and tubules in the kidney showing deposition of eosinophilic material

Fig. 8: Bone marrow aspiration showing deposition of erythroid, myeloid cells with normal maturation and scattered plasma cells

Fig. 9: Congo red under polarization showing apple green birefringence

Cardiac MRI

I

Fig. 4: 2 chamber image showing increased end diastolic left ventricular wall thickness

left ventricular hypertrophy, increased myocardial echogenecity ?infiltrative cardiomyopathy ?amyloidosis, LA high normal, mild MR and trace TR, Grade 1 diastolic dysfunction (E/E’ >15) and minimal pericardial effusion and no intracardiac clot/vegetation (Figures 1, 2, 3).

He was advised a cardiac MRI which revealed left ventricular concentric h y p e r t r o p h y s h o w i n g d i f f u s e d e l a ye d e n h a n c e m e n t c o n s i s t e n t with amyloidosis, normal LV systolic function, bilateral minimal pleural effusion, mild MR and trace TR (Figures 4, 5, 6). In view of continuing proteinuria,

he was advised a kidney biopsy. The biopsy showed nephrotic syndrome with AL amyloidosis (Figure 7). Bone marrow aspiration was also done to rule out Multiple myeloma showed focal marrow lymphoplasmacytosis (focally increased lymphocytes upto 60% and focally increased plasma cel ls upto 6-8%) (Figure 8) . Bone marrow biopsy was advised. Bone marrow immunof ixa t ion showed hypercellular marrow for age with scattered plasma cells . Congo red staining showed typical apple green birefringence (Figure 9). Patient was given symptomatic treatment in form of diuretics and planned for traditional chemotherapy.

Discussion

Amyloidosis is a systemic disease described by Rudolph Virchow in

1854. AL Amyloidosis (earlier called Primary Amyloidosis) is a light chain disease of the bone marrow affecting men more than women and age group 50-80 years of age. It is rare with an incidence of 8.9 per million population.3 The plasma cells, a subgroup of white blood cells makes antibodies which are proteins or immunoglobulins. The immunoglobulin has a basic structure of heavy and two light chains. The light chains (kappa and lambda) get free from an antibody and misfold.

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AL may be associated with myeloma as they both affect the plasma cells. According to a study, there was no difference in the clinical manifestations of primary amyloidosis , myeloma associated amyloidosis and secondary amyloidosis but kidney was the major site of involvement.4 The prognosis in systemic amyloid disease and nephrosis was found to be better.4 Infiltration of amyloid in the heart essentially leads to restrictive cardiomyopathy with manifestations of heart failure and conduction abnormalities.5 In this case there was a conduction defect which was demonstrated in the ECG as a low voltage. The amyloid deposits were widely scattered and a distinct speckled appearance was seen. Most ly the diagnosis can be confirmed by biopsy. A study done on senile amyloidosis showed three distinct forms of cardiac

amyloidosis –senile aortic amyloid, 78% had isolated atrial amyloid and 25% had senile cardiac amyloid of ASc1 type.6 The kidney was not involved in any one of the patients. The occurrence of renal and cardiac amyloidosis is rare. Conclusion

Cardiac and renal amyloidosis is a rare finding. The presentation was unique and posed a diagnostic challenge. Prognosis of AL chain amyloidosis is poor and mortality is high. The patient died after two months of confirmed diagnosis . Ear l ier diagnosis with therapeutic interventions portends a better response to current therapy and prolonged survival.

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