JRSM >
Volume 95, Number 9 >
Pp. 459-460
Centre for Nephrology, Royal Free and University College Medical School,
Bland Sutton Institute, Middlesex Hospital, Mortimer Street, London W1N 8AA,
UK
1 Department of Rheumatology, Whipps Cross Hospital, Whipps Cross Road, London
E11 1NR, UK
Correspondence to: Dr Hamish Dobbie E-mail: hamish.dobbie{at}ucl.ac.uk
Acute localized scleroderma (morphea) can present as severe generalized oedema with rapid weight gain and oliguria. The putative mechanism is increased capillary permeability.
CASE HISTORY
A woman of 67 was referred to the renal service for investigation of severe and increasing peripheral oedema which had not responded to treatment with diuretics. Her weight had risen by 12 kg in a few weeks. On close questioning she indicated that the skin of her swollen legs had become abnormal in texture, ‘hard’, and she had also noticed hardening of the skin of the forearms and lower abdomen. 7 years previously seronegative rheumatoid arthritis had been diagnosed, mainly affecting her hands; this had responded to weekly methotrexate, which she was still taking.
There was sacral and pretibial oedema, with abdominal swelling; the lungs were normal and jugular venous pressure was not raised. She had striking dermatographia, acrosclerosis and hardening of the skin of both legs. Dipstick testing of urine revealed neither proteinuria nor haematuria. On admission, plasma sodium was 138 mmol/L, potassium 3.9 mmol/L, albumin 28 g/L, urea 4.7 mmol/L and creatinine 76 µmol/L. C-reactive protein was 70 mg/L. Haemoglobin was 11.9 g/L with normal white cell count and differential; platelet count was 454x109/L. Results of the following were all normal: plasma glucose, calcium, phosphate, bilirubin, alanine aminotransferase, alkaline phosphatase, immunoglobulins and protein electrophoresis, and complement C3 and C4; clotting tests; thyroid function tests; bone marrow biopsy; and abdominal CT scan (apart from generalized oedema). An echocardiogram showed normal left ventricular function but there was some dilatation of the right ventricle with moderate tricuspid regurgitation. Initial urine volume was only 500 mL/day, though creatinine clearance was normal. Albuminuria remained undetectable, but she had tubular proteinuria; 24-hour urinary sodium excretion was very low (12 mmol/24 h) and remained so for several weeks; urine osmolality was 982 mosm/kg, with plasma osmolality 294 mosm/kg. Colloid oncotic pressure was slightly reduced at 19 mmHg (normal range 20-23). After admission she gained a further 20 kg (about 1 kg/day), despite fluid restriction. Further investigations showed serum aldosterone normal, renin about twice the upper limit of normal, rheumatoid factor negative, antinuclear antibody (ANA) weakly positive at 1:20, anti Ro, La, Sm, RNP, Jo-1 and SCL070 all negative. Urinary cortisol was normal.
A diagnosis of morphea was suggested and was confirmed by skin biopsies. She was treated first with methylprednisolone, then with oral steroids and a trial of penicillamine. The skin disorder stabilized and the oedema subsided over a few months. Renal function, which did not change during the hospital admission, remained stable during 2 years of follow up with plasma creatinine around 90 µmol/L and an isotopic glomerular filtration rate of 60 mL/min/m2. She has required treatment for hypertension, currently well controlled on two drugs. Her albumin and haemoglobin are now normal. There has been no recurrence of the peripheral oedema.
COMMENT
This patient seems to have had a widespread increase in capillary permeability in association with her acute morphea, triggering avid renal sodium retention. The case is unusual in that the patient was not particularly unwell (in contrast to patients with ‘capillary leak syndrome’, who are usually very sick and hypotensive, even shocked1), and the onset of the syndrome was gradual. The oedema was caused by increased dermal capillary permeability, which led to a barely evident reduction in circulating volume. The renal response was to conserve salt and water, explaining the persistently low urinary volumes and low urinary sodium. The high plasma renin levels also reflect volume depletion.
Morphea can be localized or, as in this case, widespread. It is more common
in women than men and in most cases is associated with ANA positivity. The
condition is distinguished from scleroderma by the absence of Raynaud's
phenomenon and systemic disease. Morphea on the background of seronegative
rheumatoid arthritis is unusual, and perhaps this case should be viewed as an
‘overlap syndrome’. In scleroderma oedema is a recognized
complication, and there is evidence of abnormal microvasculature in this
condition with broadening and splitting of the basal lamina of
capillaries2. During
the oedematous phase of both morphea and scleroderma, concentrations of
certain cytokines are high, subsiding as the disease moves to a more chronic
phase3. These
cytokines are probably the cause of the abnormal capillary permeability and
oedema. Tubular proteinuria, which was present in our patient, has been
reported in association with high levels of circulating cytokines in other
inflammatory
diseases4. Oedema,
either localized or generalized, is commonly seen in the rheumatic diseases
and presumably likewise results from a cytokine-induced vascular leak. In
dermatomyositis the oedema may be localized around the eyes or may be
generalized, with substantial weight
gain5. In rheumatoid
arthritis, localized limb oedema is a well-known phenomenon; it has also been
reported in systemic lupus
erythematosus5 and
diffuse systemic
scleroderma6. In
many cases it responds well to treatment with steroids. Widespread systemic
vascular leakage is seen in patients treated with interleukin 2, interferon
and immunotoxins, and commonly it is the dose-limiting factor in these
treatments7.
Spontaneous ‘systemic capillary leak syndrome’ is very rare and
tends to be associated with monoclonal gammopathy, which was excluded in our
patient; in this syndrome there is episodic severe hypotension and
haemoconcentration as well as profound
hypoalbuminaemia1.
The primary cause seems to be a circulating toxic factor that increases
capillary permeability, perhaps by causing endothelial cell
apoptosis8.
The treatment of scleroderma is made difficult by the variability of its natural course and uncertainty as to its pathogenesis9. Immunosuppressant agents such as methotrexate have been used, with encouraging results in one small trial10. Because our patient's symptoms developed while she was taking methotrexate, she was treated initially with the antifibrotic agent penicillamine. Spontaneous improvement of scleroderma/morphea is well recognized, so we cannot be sure that the course of her illness was affected by the treatment.
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