Physicians in Japan put on their detective caps to piece together why two seemingly uninjured men developed muscle swelling so severe that their respective arm and leg nearly rotted from the inside out.

According to their investigation in BMJ Case Reports, the doctors ultimately landed on an unlikely culprit: venom from a diminutive venomous snake whose delicate bites may go unnoticed.

Acute compartment syndrome (ACS) arises when fluid rapidly accumulates within a muscle compartment; a section of muscle fibers, nerves, and blood vessels that are bound by a fibrous membrane called fascia. Normally, the body can drain excess fluid from a compartment, but in certain instances – most commonly in response to extreme injury or blood vessel rupture – the pressure builds so suddenly that the veins draining de-oxygenated blood from the tissue are obstructed, leading to a disastrous positive feedback loop of increasing fluid retention.

In all instances, ACS is a medical emergency because irreversible loss of muscle function, stemming from lack of oxygen and accumulation of toxic cellular waste chemicals, onsets within 4 to 12 hours. Tissue necrosis and permanent damage to the kidneys can also occur.

Though the underlying cause will require separate treatment, alleviating the ACS itself is fairly straightforward – just cut into the fascia and relieve the pressure, a procedure called a fasciotomy.

The report's first case, seen in 2016, unfolded when a 38-year-old man came into an emergency room complaining of severe pain and swelling in his arm and double vision that had begun after he fell in his backyard. Scans showed that no bones had been broken and nor were any blood vessels leaking. Curiously, evidence of impaired blood clotting was found.

Unable to determine the cause of the ACS, the patient was treated with a fasciotomy, antibiotics, and kidney support.

Looking through past medical records, the physicians came upon another unsolved case with eerie similarity. In 2008, a 42-year-old was treated for ACS in his leg after suffering a non-serious tumble in the gutter.  

Because both these patients’ diagnosis of ACS could not be pinned to any obvious cause, the medical team focused on the unusual shared symptoms of oculomotor nerve palsy and low blood platelet counts.

Putting all the pieces together, they concluded that “the two cases described herein were atraumatic ACS secondary to mamushi (Gloydius blomhoffii) bite."

"However, a diagnosis could not be established owing to the lack of bite marks and clinical history of bite.”

Mamushi is a species of pit viper found throughout Japan. Preferring to stay hidden in the undergrowth, they bite readily when threatened. Yet thanks to their thin fangs, the attack feels more like an insect sting and bite marks escape detection. Mamushi venom is known to cause temporary oculomotor nerve palsy, rapid cell injury, and prevent blood clotting. According to the authors, if a patient is not treated with antivenom, damage to blood vessels and muscle cells can cause onset of ACS.

Thankfully for both these patients, who went on to make full recoveries, it appears that the fasciotomies performed helped flush the venom out of the tissue before it could cause further damage.