Diagnosis and Discussion

Diagnosis

Colchicine toxicity

Discussion

Colchicine is a tricyclic alkaloid that is often used to treat crystalline arthropathies, such as gout, and many other medical conditions, including pericarditis. The drug achieves its effect by binding to tubulin and inhibiting polymerization, thus dampening the inflammatory processes, by inhibition of degranulation, chemotaxis, and mitosis [1]. Besides binding to tubulin, colchicine also preferentially binds to two other proteins, CYP3A4 and P-glycoprotein, which are responsible for colchicine metabolism. Colchicine has a long clinical half-life of 20 to 40 hours. Thus, individuals who have altered levels of expression of CYP3A4 and P-glycoprotein, renal failure, or liver diseases are prone to colchicine toxicity. As CYP3A4 and P-glycoprotein also interact with various other medications, colchicine’s toxic effect are also observed in patients who are concurrently on other medications (such as calcium channel blockers, certain antibiotics, and certain selective serotine reuptake inhibitors) [1].

As colchicine mostly affects areas with rapid cell turnover, patients with colchicine toxicity often present with gastrointestinal symptoms, such as abdominal pain, cramping, and diarrhea. Other clinical manifestations, such as bone marrow suppression or alopecia, may also be seen [2]. Histologically, colchicine toxicity demonstrates, numerous metaphase ("ring" form) mitoses), increased apoptotic bodies, epithelial stratification, and loss of nuclear polarity [2]. The latter two findings may be striking and mimic dysplasia, however, lack of atypia and appropriate surface maturation enable correct distinction. These characteristic features are often seen best in the duodenum and gastric antrum [2]. The treatment of choice is medication withdrawal with supportive care.

Similar histologic findings can also be seen in patients on taxane chemotherapeutic agents which is the main differential diagnosis to consider. These agents are commonly used to treat solid organ malignancies such as breast cancer. Taxanes have a similar mechanism of action to colchicine, in that they also interfere with tubulin and inhibit polymerization causing mitotic arrest. Thus histologically, "ring" mitoses are also seen with this drug along with increased apoptosis. Clinical correlation is essential in distinguishing between these two drug classes as the morphologic findings are indistinguishable based on histology alone and the clinical implications are paramount. The changes seen with taxanes, unlike colchicine, do not necessarily indicate toxicity and thus correlation with the patient’s clinical status is required [3, 4].

References

Slobodnick, A., et al., Colchicine: old and new. The American journal of medicine, 2015. 128(5): p. 461-470.

Iacobuzio-Donahue, C.A., et al., Colchicine Toxicity: Distinct Morphologic Findings in Gastrointestinal Biopsies. The American Journal of Surgical Pathology, 2001. 25(8).

Marginean, E.C., The Ever-Changing Landscape of Drug-Induced Injury of the Lower Gastrointestinal Tract. (1543-2165 (Electronic)).

Daniels, J.A., et al., Gastrointestinal Tract Epithelial Changes Associated With Taxanes: Marker of Drug Toxicity Versus Effect. The American Journal of Surgical Pathology, 2008. 32(3).

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