PSEUDOXANTHOMA ELASTICUM PRESENTING AS HAEMATURIA – A CASE REPORT

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ABSTRACT:

          Pseudoxanthoma elasticum is a rare inherited disorder of connective tissue, characterized by general elastorrhexis of the elastic tissue in the dermis, the blood vessels and Bruch membranes of the eye.

KEYWORDS:

          Pseudoxanthoma elasticum (PXE), Angioid streaks, Bruch’s membrane, Connective tissue, Haematuria.

CASE REPORT:

          A 55 years Hindu female presented with complain of recurrent haematuria for 6 months, diminished vision for one year and weakness of left half of the body since 3 years. She had attended menopause and was under Enalapril (5 mg) since 1 year for hypertension. No history of diabetes, tuberculosis or CAD. No suggestive family history.

          On examination the patient was of average built with BP 130/80mmHg (both upper limbs) , pulse rate 80/min, regular (Brachial) good volume while diminished pulsation of both radial, ulnar, posterior tibial and dorsalispedis arteries. Both carotids, axillary, femoral and popliteal artery pulsations were well felt. She was mild anaemic without icterus, cyanosis, clubbing or lymphadenopathy. JVP was not raised. Thyroid was normal. Chest examination revealed vesicular breath sounds without any added sounds. Cardiovascular system examination revealed normal apex with normal heart sounds, without any murmur. P/A examination was normal without any renal brui. On CNS examination the cranial nerves, motor, sensory systems were normal without any cerebellar signs or meningeal signs. On examination of the skin, there were laxed skin with yellowish Xanthomatous lesions over neck and upper chest (Fig. 1, 2). Eye examination revealed vision 6/9 (Lt) and 6/6(Rt) and fundoscopy showed macular choroiditis with angioid streaks on left side (Fig. 3).

Routine Investigation Showed: FBS - 82mg%, PPBS – 104mg%, Blood Urea 20 mg%, Serum Creatinine 1.08mg%, ESR - 20mm/1 hour, DC N⁷², L²⁵, E³, M⁰, B⁰, and TLC - 8000/mm³, Lipid Profile of serum were Sr. Total cholesterol -160mg%, TGS -108mg%, HDLC -48mg%, LDLC- 92mg% and VLDL-C -21mg%, Urine analysis showed proteinuria(+) and 10-15 RBC/HPF and RBC casts. Mantoux test was 18mm , ECG was normal.

ECHO Showed:  Mitral value thickened, EF – 65%, Aorta – 32 mm, MACS – 17 mm, LA – 42mm.

Skin Biopsy Revealed:  Epidermis was normal and dermis showing accumulation of basophilic mucoid material and collagen bundles. There was occasional macrophages and multinucleated giant cells compatible with pseudoxanthoma elasticum.

Colour Doppler study of kidney and renal arteries showed normal kidney size , shape, echo structure and punctate calcific areas on both renal cortex. Both renal arteries and interlobar arteries and aorta showed normal Doppler profile.

Doppler study of upper and lower limb arteries showed:-

Upper Limb: B/L subclavian , axillary, brachial , radial , ulnar arteries were anechoic with normal caliber and showing loss of normal triphasic blood flow with low resistance blood flow in them.

Lower limb: B/L femoral , popliteal and dorsalis pedis arteries were normal caliber with speaks of arterial calcifications seen in arterial wall at places and with loss of normal triphasic blood flow with low resistance.

Aorta and iliac arteries: Showed normal in caliber and size with normal spectrum of blood flow and no thrombus or stenosis. The patients was diagnosed to be a case of Pseudoxanthoma Elasticum with complications leading to peripheral vascular , renal and retinal involvement.

Treatment given: Capsule E, Tab Pentoxyphyllin and advised diet restriction , regular follow up.
 

DISCUSSION:

          Pseudoxanthoma elasticum is a rare disease occurring in about 1 in every 160,000 population. Females are frequently affected. The basic defect lies in the elastic tissue. Typically it is first noticed during adolescence as yellow orange bumps on the side of neck. This entity has been observed in India and has been reported sporadically from all regions.

Aetiology:

          Pseudoxanthoma elasticum is caused by genetic mutations that are inherited in either a dominant or recessive mode. A person with recessive form of the disease (most common) must posses two copies of the PXE gene to be affected, and therefore must have received one from each parent. In dominant form , one copy of the defective gene is sufficient to cause the disease.  In some cases, a person with dominant form inherits abnormal gene from a parent with PXE, more commonly, the mutation , arise as a spontaneous change in the genetic material of the affected person.  These cases are called “ Sporadic” and do not affect parents or sublings , although each child of a person with sporadic PXE has a 50% risk to inherit the condition. 

          Actual genetic defect is caused by different mutations or deletion in a single gene called ABCC-6 (also known as MRP6) located on chromosome 16. Although responsible gene has been identified, how it causes PXE is still unknown¹.

          It has been suggested that defects on glycosaminoglycans or proteoglycans might play a role in pathogenesis, bends of chondroitin sulphate, dermatan sulphate and hyaluronic acid are increased in the areas of calcification².       

          An abnormality in cysteine proteinase of the fibroblasts has been demonstrated. It seems likely that an abnormal glycosaminoglycan secreted by fibroblasts is deposited on the surface of the elastic fibres and leads to fragmentation and calcification.
 

Pathology:

          In skin lesions the elastic fibres in the mid dermis are clumped, degenerated, fragmented and swollen and abnormal fibres stains positively for calcium. The collagen fibres are also abnormal being split into small fibres. Similar changes occur in connective tissues of the media and intima of blood vessels, Bruch membrane of the eye and the endocardium and pericardium. Calcification has been reported in pulmonary and other visceras³. 

          Vascular involvement is generalized but may involve predominantly the larger arteries, the mesenteric , renal and visceral arteries or those of the extremities. Calcification of internal elastic lamina of the arteries leads to vascular obstruction.

CLINICAL FEATURES:

Skin changes: Lesion are small (1-3 mm in diameter), yellowish papule arranged on linear or reticular pattern and eventually forming plaques. Telangiectasia may be present. Areas involved are – fold of groin, arms, neck, axillary folds, armpits, perineum and mucous membrane. Skin is soft, lax, wrinkled and may hang in folds.

Eye: Angioid streaks represent defect or cracks in Bruch’s membrane. Angioid streaks are irregular jagged, curvilinear lines that radiate from the region of the optic nerve into the more peripheral retinal tissue. Other findings in PXE include salmon spots (areas of tissue atrophy) optic disc drusen (calcified deposits  within the optic nerve head) and crystalline bodies (small yellow round subretinal lesions) and choroids neovascularization presented  with visual loss (70%). If haemorrhage and choroiditis develops it may lead to blindness⁴.

Cardiovascular Changes:

·        There may be intermittent claudication, diminished peripheral pulses, accelerated altheroma with hypertension⁵.

·        Death commonly result from cerebral haemorrhage, coronary occlusion (angina/MI) or massive haemorrhage into the gut⁵.

·        Cardiomyopathy and mitral value prolapse (5-8%) has been reported.

Associated abnormalities: May be associated with Osteitis deformans (Pagets disease) Osteoectasia, sickle cell disease, Marfan’s Syndrome and perforating elastosis. 

Diagnosis:

          Diagnostic criteria for Pseudoxanthoma elasticum (from Lewohl et al)⁶.

Major Criteria:

1.     Flexural yellow cobblestone lesions.

2.     Characteristic histopathological features of lesional skin using elastic tissue and calcium stains (e.g Van Gieson and Von Kossa).

3.     Angioid streaks in the retina.

Minor Criteria:

1.     Characteristic histological changes in non-lesional skin.

2.     Family history of PXE in first degree relatives.

·        It should be suspected in cases without skin lesions by obliterative arterial disease of early onset and unexplained gastrointestinal haemorrhage.

Management:

·        The important aspect of treatment is to ensure that complications from blood vessels involvement are prevented or dealt with speedily by the appropriate specialist.  Regular follow up with a specialist vascular surgeon and/or cardiologist is recommended.

·        There is currently no effective treatment for skin lesions, but the appearance may be improved by plastic surgery.

·        Restriction of dietary calcium has been tried with some benefits , but controversial.

·        Laser photocoagulation, may be helpful in preventing further bleeding at the back of the eye.

·        Genetic counseling may be helpful.

·        Propranolol – to prevent development of aortic dilatation.
 

CONCLUSION:

          Though incidence of haematuria is reported earlier in some cases, our case primarily presented with haematuria along with other usual complications. The probable mechanisms is due to microvascular involvement of kidney and urinary tract.

REFERENCE:

1.           L Frank Glass/Shelli Marks, BS: Department of Internal Medicine and Pathology, Vuniversity of South Florida College of Medicine –Nov 2003 – 05.

2.           Pasquali – Ronchette L, Pincellinc et al – Arch dermatol. Res 1986, 278, 386-92.

3.           Goodmen RM, Simth E W, Paton D et al – “PXE”: Clinical and histopathological study medicine, 1963, 42, 297- 334.

4.           Vitreous –Retina – Macula Consultant of New York – Angioid streaks and pseudoxanthoma elasticum.

5.           Parker J C, Firedman –Kien AE, Levin et al . NEJM 1964/Kundrotus L, Novak J et al ; GI bleeding in PXE Am J Gastroenterol , 1988.

6.           Lebwohl et al ; J Am Aacd Dermatol, 1994.