A Reassessment of Topical Organic Phosphorus Insecticide Exposures and Permanent Paralysis

To the Editor:

We write to express several concerns following our review of a recent case report regarding the potential for an organic phosphorus compound to induce peripheral neuropathy following a possible dermal exposure [1]. While it is true that organic phosphorus compounds have been reported to cause both acute and delayed peripheral neuropathy, the conclusions in this case report are not substantiated by the information provided.

The initial presentation of this patient may not even be related to the pesticide exposure. The time course to the onset of the illness after the exposure was not specified. The potential contact with the agent was brief (about 15 minutes) and via a dermal route (the potential for inhalation is uncertain from the records). While many organic phosphorus compounds can be absorbed topically, chlorpyriphos is poorly absorbed through intact skin with one study suggesting less than 5% of a topical dose is bioavailable [2]. Solvents such as xylene may enhance dermal absorption of the compound; however, severe systemic cholinergic toxicity and permanent neurologic injury after a 15‐minute application is unlikely even if there was a potential for inhalational exposure. When adequate decontamination is performed as described in this case, the absolute amount absorbed may be even less.

Second, the permanence of this patient's symptoms as noted in the report suggests organic phosphorus compound delayed peripheral neuropathy (OPIND). However, the time course in this case is not typical for OPIND, the type of organic phosphorus‐induced neuropathy thought to result from inhibition of neurotoxic esterase (NTE). Most classic descriptions of NTE inhibition in humans leading to long‐lasting or permanent neuropathies have occurred from exposures to non‐insecticidal compounds that do not affect acetylcholinesterase, such as triorthocresyl phosphate (TOCP). In these cases and others involving insecticides, the onset of peripheral signs and symptoms occurs over days to weeks [3]. Patients with significant acute exposures to organic phosphorus compounds can present with rapid onset of weakness and paralysis from excess acetylcholine at the neuromuscular junction, but this has not been reported to occur with normal cholinesterase levels due to the severity of poisoning required. In addition, if this patient's initial symptoms resulted from early cholinesterase inhibition at motor end‐plates, we would have expected this to improve or resolve over the ensuing days to weeks as cholinesterase activity recovered. Incidentally, chlorpyrifos has much greater activity for acetycholine inhibition than for NTE inhibition [3], and to our knowledge there has never been a well‐documented case of acute exposure to this compound leading to delayed or permanent neuropathy that did not result in significant reductions in measured cholinesterase activity. A previous case series cited in this case report suggested that a sensory neuropathy was associated with chlorpyrifos exposure; however, review of the cases presented reveals that most were chronic exposures with limited documentation of the exposure except by history, and most had a delayed presentation of the their complaints with eventual complete resolution [4].

Interestingly, the red blood cell cholinesterase activity in this patient was measured 4 days after the exposure and was normal. We agree that “normal” cholinesterase activity may be seen in individuals with preexisting elevated activity (i.e. congenital or in patients with nephrotic syndrome), but for a patient who is poisoned to such a severe degree that they present with this extent of weakness, paralysis, and cholinergic findings to display normal red blood cell cholinesterase activity four days later has again not been reported to our knowledge. We would expect red blood cell cholinesterase activity to be relatively close to “unmeasurable” or significantly depressed even four days after the exposure if the patient was paralyzed as rapidly in the course of their illness as this case report suggests.

Another apparent inconsistency in this report is the patient's rapid onset of urinary retention. While nicotinic symptoms can complicate the presentation of acute organic phosphorus poisoning, the nicotinic symptoms generally progress into more cholinergic findings as the poisoning continues, and certainly should resolve once cholinesterase activity recovers. His retention has persisted over 10 years after presentation.

Finally and perhaps most importantly, other etiologies for this patient's symptoms were not discussed or evaluated. Acute onset weakness, urinary retention, and some autonomic findings are also consistent with disorders such as multiple sclerosis. The persistence of his complaints after ten years would also be typical of this and other illnesses. This patient's lack of work up, including electrophysiologic studies (electromyography, nerve conduction studies), magnetic resonance imaging and lumbar puncture makes the diagnosis uncertain. Sorting out these issues and the various other differential diagnoses is the cornerstone of value in engaging a medical toxicologist early in the course of these confusing cases. For these reasons, attributing this individual's symptoms to an organic phosphorus exposure ten years prior seems premature at least, and probably inaccurate.

Sincerely,

Richard F. Clark, M.D.

Saralyn R. Williams, M.D.

Frederick Fung, M.D.

Aaron B. Schneir, M.D.

Binh T. Ly, M.D.

David A. Tanen, M.D.

Stephen W. Munday, M.D.

UCSD Division of Medical Toxicology

San Diego, CA