Neurofibromatosis-1 with bilateral partial radial artery stenosis.

Not much attention is paid to vascular complications in neurofibromatosis-1 (NF-1) though they are well known to occur. A case of vascular NF-1 with bilateral partial radial artery stenosis resulting in digital gangrene involving fingers of both hands is being reported here. Various vascular abnormalities in NF-1 as complications resulting from them and their management is briefly highlighted.

INTRODUCTION

Neurofibromatosis is an autosomal dominant neurocutaneous disorder which affects 1 in 3000 individuals. Vascular complications in neurofibromatosis-1 (NF-1) are not uncommon. However, many of these abnormalities may not be evident clinically. One of the causes for hypertension in these patients is renal artery stenosis, and the other is pheochromocytoma.[1] A case of late onset NF-1 with bilateral partial radial artery stenosis resulting in digital gangrene is being reported.

CASE REPORT

A 35-year-old male, product of a nonconsanguineous marriage, manual embroidery maker by profession, presented with painful ulcers involving thumb and index fingers of both hands for 3 months. He did not drink alcohol but was a smoker (3-4 cigarettes/day) since 20 years. None of his family members suffered from similar illnesses. There was no history of Raynaud's phenomenon.

General and systemic examinations were unremarkable. He had average level of intelligence. Pulsations of the Right radial artery could not be felt and left radial artery pulse was feebly felt. Cutaneous examination revealed multiple neurofibromata and cafe au lait spots over back [Figure 1]. Palmar freckling [Figure 2] and axillary freckling [Figure 3] were also seen. Thumb and index fingers exhibited dry gangrene at finger tips [Figure 4].

Figure 1

Cafe Au Lait Spots and cutaneous neurofibromata over patient's back

Figure 2

Palmar freckling

Figure 3

Axillary freckling

Figure 4

Gangrene involving tip of thumbs and index fingers

Differential diagnoses included vascular NF-1, thromboangitis obliterans (TAO), CREST syndrome, and antiphospholipid syndrome (APS). However, there was no history of pain at rest, intermittent claudication, and ischemic ulcerations. Thrombophlebitis was absent. Papa scoring also did not favor the diagnosis of TAO.[2] Patient could not afford arteriography which could have been helpful.

His complete blood count was normal and VDRL was nonreactive. Estimation of ANA, Anti phospholipid antibodies (APLA), cryoglobulin, and homocysteine levels could not be carried out as the patient was extremely poor.

Cervical X-ray did not reveal cervical rib. X-rays of skull and spine were normal. Ultrasound examination did not detect any mass per abdomen. Arterial color Doppler detected bilateral partial radial arterial stenosis. A computed tomography (CT) angiogram could not be performed. Fundus examination showed the presence of Lisch nodules in the right eye. Skin biopsy was consistent with diagnosis of cutaneous neurofibroma. The patient was diagnosed to have vascular NF-1 with partial radial artery stenosis, after Buerger's disease, CREST syndrome, and anti phospholipid syndrome were ruled out with available clinical findings and investigation results.

The patient was advised to quit smoking and keep his hands warm. He was treated with oral pentoxifylline (400 mg twice daily) and aspirin (150 mg/day). The wounds were dressed regularly. He was advised to get regular ophthalmological examinations for early detection of a possible optic nerve pathway tumor.

DISCUSSION

Though not obvious clinically, vascular anomalies have been reported in nearly 50% of autopsies[3] of patients suffering from NF-1. Apart from kidneys, vascular lesions are seen in intracerebral vessels, those of heart, endocrine glands, gastrointestinal tract, the pancreas, and spleen.

These vascular changes are believed to be due to proliferation of Schwann cells within arteries with secondary degenerative changes and fibrosis.[4] The pathology of the lesions is divided into four types, namely (1) intimal, (2) advanced intimal proliferation occluding lumen, (3) aneurysmal form (fibrohyaline thickening of intima with fragmentation of muscularis and elastica) and (4) nodular form (spindle and epithelioid cells disturbing integrity of vessel walls).[5] Two basic categories have also been described: one involving large vessels with surrounding neurofibromatous or ganglioneuromatous tissue, the other being dysplasia involving small vessels.[6]

In our patient, Buerger's disease (TAO) was considered an important differential diagnosis. However, in color Doppler, there was no thrombophlebitis as TAO is a pan vasculitic condition.

In TAO, arteriography changes include thrombosis in the lumen, vessel being normal proximally, corkscrew collaterals and thrombophlebitis of adjacent veins. Biopsy findings show luminal thrombosis with inflammatory infiltrate with intact internal elastic lamina.

In NF-1, angiography reveals aneurysm, stenosis, and arteriovenous malformations. Biopsy changes reported in NF-1 are as follows: adventitia surrounded by neurofibromatous or ganglioneuromatous tissue, thinning of media, fragmentation of elastic tissue, and intimal hyperplasia.

Detailed study of NF-1-associated vasculopathy has been carried out. Different anomalies and their management have been described in this article.[7] Severe systemic vasculopathy in a 4-year-old boy with NF-1 has also been reported.[8] Gangrene in child has been documented.[9] Radial artery aneurysm has been described earlier.[10] We are reporting radial artery stenosis which has not been reported earlier. A CT angiogram would give a better insight. Percutaneous transluminal angioplasty would be a better treatment option in the management of stenosis.[11]

The aim of this report is to highlight various life-threatening vascular complications reported in NF-1, to detect them early and treat them to prevent lethal complications.