Parkes-Weber syndrome in the emergency department

Background

Parkes-Weber syndrome is a rare genetic disease with an unknown prevalence presenting with pathological capillary malformations and arteriovenous malformations affecting the same limb.1 The aetiology is due to a spontaneous or inherited RASA1 gene mutation involved in the development of the vascular system.1 At birth or during childhood, the capillary malformations clinically present as portwine stains, whereas the arteriovenous malformations present as hemihypertrophy, resulting in length/circumference discrepancies and spontaneous swelling associated with pain. The most significant life-threatening complication is high-output heart failure secondary to the arteriovenous malformations, resulting in cardiomegaly and pulmonary oedema.2

Another syndrome commonly confused with Parkes-Weber syndrome is Klippel-Trenaunay syndrome, as both are associated with capillary malformations (portwine stains), hemihypertrophy and a deep tissue malformation. They can be distinguished, however, by the difference in appearance of the portwine stains and by the type of deep tissue malformations. The portwine stains of Parkes-Weber syndrome are salmon-coloured, in contrast to dark purple in Klippel-Trenaunay syndrome3 4; and the deep malformations of Parkes-Weber syndrome are arteriovenous malformations, whereas those in Klippel-Trenaunay syndrome are venous malformations.1 Therefore, although both syndromes have similarities, the symptoms and treatments are vastly different.

Case presentation

A 20-year-old woman with no relevant previous medical history presented to the emergency department (ED) with 1 day of painful, acute worsening of her chronic left thigh swelling without an identifiable trigger. She denied additional symptoms, trauma, personal and family history of thrombosis or coagulopathy, and tobacco or illicit substance use. A routine workout 2 days prior was unchanged from her usual described intensity. The pain was described as ‘tightness’, which was relieved by rest and aggravated by movement. The patient reported that her chronic asymmetry was never investigated by previous physicians because it was only slightly wider in girth and non-painful since childhood. Her only prescribed medication was a levonorgestrel intrauterine device, and family history was significant for ulcerative colitis and coronary artery disease.

The physical examination revealed her to be in no acute distress with normal vital signs. Relevant findings included a left thigh, which was roughly double the circumference, but the same length, as the right. Otherwise, both thighs had soft compartments without erythema, crepitus, warmth or tenderness to palpation (figure 1). Her neurovascular function was normal bilaterally, there was no pitting oedema or calf swelling, and no discomfort was noted behind the knee on forced dorsiflexion. Finally, no urine colour changes were noted. All other findings were either normal or not clinically relevant. Notably, capillary malformations in the patient’s left thigh had been present since birth but were not noted on the treating physician’s examination.

Investigations

The initial workup revealed a normal complete blood count, normal basic metabolic panel (including calcium, magnesium and phosphate), negative pregnancy test (qualitative human chorionic gonadotropin), elevated d-dimer at 3.25 μg/mL (normal <0.49 μg/mL) and creatine kinase at 7697 U/L (normal <200 U/L). Other studies such as uric acid level, liver function tests, prothrombin time, activated partial thromboplastin time, serum aldolase and lactate dehydrogenase were not ordered at the attending physician’s discretion. The clinician ordered a venous Doppler ultrasound of the lower extremity and consulted nephrology and orthopaedics for additional recommendations.

The lower extremity ultrasound revealed patent, compressible, bilaterally symmetric femoral and popliteal veins. It also showed soft tissue oedema in the medial left thigh. Nephrology recommended serial creatine kinase measurements to ensure downtrending levels, while the orthopaedic surgeon recommended a left femur radiograph and lower extremity MRI with and without contrast (figure 1) to evaluate for muscle or tendon tears or evidence of myositis.

The radiograph showed no acute fracture with normal femur morphology. MRI results showed left thigh subcutaneous and fascial oedema with biceps femoris and semitendinosus muscle hyperintensity (figure 2). There were no fluid collections or mass lesions and the neurovascular bundle was intact. None of the studies was noted to show evidence of arteriovenous (AV) malformation on the radiologist’s read.

Differential diagnosis

The treating clinician’s differential diagnosis included rhabdomyolysis, deep venous thrombosis, compartment syndrome, necrotising fasciitis and cellulitis. Given that the patient had no known history of chronic medical conditions, no congenital conditions were considered in the differential diagnosis.

Rhabdomyolysis was considered the most likely diagnosis due to elevated creatine kinase levels, acute onset symptoms and recent exercise. Deep venous thrombosis was ruled out with venous Doppler ultrasound. Compartment syndrome was ruled out with a normal femur radiograph. Necrotising fasciitis and cellulitis were ruled out by physical examination and lack of fluid collections on MRI.

Treatment

The patient was then received a 30 mL/kg bolus of normal saline to prevent acute kidney injury and 1000 mg IV acetaminophen. Adequate pain control was achieved with 4 mg IV morphine.

Outcome and follow-up

After discussion with orthopaedics and nephrology and an extended stay in the ED, the emergency physician and consultants determined that the patient was safe for discharge home with the diagnosis of rhabdomyolysis and a plan to follow-up with internal medicine. The reasoning included definitive exclusion of life-threatening alternative diagnoses, stable patient presentation for greater than 11 hours with improvement in swelling and pain, creatine kinase level downtrend from 7697 U/L to 1800 U/L and the ability to reliably follow-up within 2–3 days.

Over the next 6 months, she presented to the ED three times with similar reports while intermittently being seen by multiple specialists as an outpatient. In rheumatology, autoimmune diseases including myositis were ruled out. Dermatology assessed large ‘birthmarks’ on her left leg (figure 3) and referred her to interventional radiology for suspected vascular malformations. The venogram performed by interventional radiology revealed arteriovenous fistulas in the left thigh (figure 4). Parkes-Weber was then proposed as the diagnosis, and a genetic analysis revealing a RASA1 variant (Chr5(GRCh37)g.86659154_86659158del) confirmed the diagnosis. She continues to have regular follow-up with her oncologist to monitor for potential complications such as heart disease with echocardiograms, limb ischaemia with symptom reviews and aneurysms with MRIs.