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Docetaxel-induced Nail Changes – A Neurogenic Mechanism: A Case Report

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Abstract

Docetaxel is a new taxoid widely used in chemotherapy for advanced breast cancer and other solid malignancies. Painful nail changes with onycholysis occur in about 40% of docetaxel-treated patients as a prominent adverse effect. We report a patient with a complete peripheral palsy of the right arm due to advanced breast cancer with diffuse tumor infiltration of the brachial plexus. Treatment with docetaxel led to onycholysis at all extremities except the paretic hand. Sensory and motoric innervation measured by nerve conduction studies showed a complete loss of large nerve fiber function of the right arm. Function of deep mechanosensitive Aβ-fibers (quantitative vibrametry) was severely decreased, but not absent. Sympathetic reflexes (induced by deep inspiration and measured with laser Doppler flowmetry) were absent on the right side and skin temperature was decreased consistent with a complete sympathetic denervation. Small afferent fibers investigated by quantitative thermotesting revealed a total loss of thermal and pain sensation. Furthermore, iontophoresis of histamine failed to induce any axon reflex-vasodilatation indicating a complete peripheral degeneration of small fiber afferents. In summary, a severe denervation of small and large fibers of the right upper limb was revealed. These results indicate that integrity of peripheral nerves seems to be a substantial factor for docetaxel-mediated nail changes. The role of an inflammatory process in onycholysis maintained by postganglionic sympathetic terminals and nociceptive C-fiber afferents is discussed. In accordance with this hypothesis, a cyclooxygenase-2 inhibitor improved nail alterations of the non-paretic limbs.

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References

  1. Crown J, O'Leary M: The taxanes: an update. Lancet 355: 1176–1178, 2000

    Google Scholar 

  2. Goldhirsch A, Francis P, Castiglione-Gertsch M, Gelber RD, Coates AS: Taxanes as adjuvant for breast cancer. Lancet 356: 507–508, 2000

    Google Scholar 

  3. ten Bokkel Huinink WW, Prove AM, Piccart M, Steward W, Tursz T, Wanders J, Franklin H, Clavel M, Verweij J, Alakl M: A phase II trial with docetaxel (Taxotere) in second line treatment with chemotherapy for advanced breast cancer. A study of the EORTC Early Clinical Trials Group. Ann Oncol 5: 527–532, 1994

    Google Scholar 

  4. Dreyfuss AI, Clark JR, Norris CM, Rossi RM, Lucarini JW, Busse PM, Poulin MD, Thornhill L, Costello R, Posner MR: Docetaxel: an active drug for squamous cell carcinoma of the head and neck. J Clin Oncol 14: 1672–1678, 1996

    Google Scholar 

  5. Trudeau ME: Docetaxel (Taxotere): an overviewof first-line monotherapy. Semin Oncol 22: 17–21, 1995

    Google Scholar 

  6. Jacob CI, Patten SF: Nail bed dyschromia secondary to docetaxel therapy. Arch Dermatol 134: 1167–1168, 1998

    Google Scholar 

  7. Correia O, Azevedo C, Pinto Ferreira E, Braga Cruz F, Polonia J: Nail changes secondary to docetaxel (Taxotere). Dermatology 198: 288–290, 1999

    Google Scholar 

  8. Obermair A, Binder M, Barrada M, Bancher-Todesca D, Asseryanis E, Kubista E: Onycholysis in patients treated with docetaxel. Ann Oncol 9: 230–231, 1998

    Google Scholar 

  9. Flory SM, Solimando DA Jr, Webster GF, Dunton CJ, Neufeld JM, Haffey MB: Onycholysis associated with weekly administration of paclitaxel. Ann Pharmacother 33: 584–586, 1999

    Google Scholar 

  10. Hussain S, Anderson DN, Salvatti ME, Adamson B, McManus M, Braverman AS: Onycholysis as a complication of systemic chemotherapy: report of five cases associated with prolonged weekly paclitaxel therapy and review of the literature. Cancer 88: 2367–2371, 2000

    Google Scholar 

  11. Wasner G, Hilpert F, Baron R, Pfisterer J: Clinical picture: nail changes secondary to docetaxel. Lancet 357: 910, 2001

    Google Scholar 

  12. Claus D, Mustafa C, Vogel W, Herz M, Neundörfer B: Assessment of diabetic neuropathy: definition of norm and discrimination of abnormal nerve function. Muscle Nerve 16: 757–768, 1993

    Google Scholar 

  13. Low PA, Neumann C, Dyck PJ, Fealey RD, Tuck RR: Evaluation of skin vasomotor reflexes by using laser Doppler velocimetry. Mayo Clin Proc 58: 583–592, 1983

    Google Scholar 

  14. Bosley PG: The concept of a capillary unit and the probable relationship of a nerve fiber, and related tissues, to the capillary in the human nailfold. Bibl Anat 7: 314–324, 1965

    Google Scholar 

  15. Jänig W, McLachlan EM: Neurobiology of the autonomic nervous system In: Mathias CJ, Sir Bannister R (eds) Autonomic Failure-A Textbook of Clinical Disorders of the Autonomic Nervous System. Oxford University Press, Oxford, 1999, pp 3–15

    Google Scholar 

  16. Bini G, Hagbarth KE, Hynninen P, Wallin BG: Thermoregulatory and rhythm-generating mechanisms governing the sudomotor and vasoconstrictor outflow in human cutaneous nerves. J Physiol (Lond) 306: 537–552, 1980

    Google Scholar 

  17. Ando Y, Araki S, Shimoda O, Kano T: Role of autonomic nerve functions in patients with familial amyloidotic polyneuropathy as analyzed by laser Doppler flowmetry, capsule hydrograph, and cardiographic R-R interval. Muscle Nerve 15: 507–512, 1992

    Google Scholar 

  18. Beck JS, Abbot NC, Samson PD, Butlin CR, Grange JM, Cree IA, Forster A, Khan F: Impairment of vasomotor reflexes in the fingertips of leprosy patients. J Neurol Neurosurg Psychiatry 54: 965–971, 1991

    Google Scholar 

  19. Schüller TB, Hermann K, Baron R: Quantitative assessment and correlation of sympathetic, parasympathetic, and afferent small fiber function in peripheral neuropathy. J Neurol 247: 267–272, 2000

    Google Scholar 

  20. Fruhstorfer H, Lindblom U, Schmidt WC: Method for quantitative estimation of thermal thresholds in patients. J Neurol Neurosurg Psychiatry 39: 1071–1075, 1976

    Google Scholar 

  21. Yarnitsky D, Ochoa JL: Warm and cold specific somatosensory systems. Psychophysical thresholds, reaction times and peripheral conduction velocities. Brain 114: 1819-1826

  22. Baron R, Saguer M: Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 116: 1477–1496, 1993

    Google Scholar 

  23. Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, Gries FA: Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med 9: 166–175, 1992

    Google Scholar 

  24. Baron R, Häbler HJ, Heckmann K, Porschke H: Respiratory modulation of blood flow in normal and sympathectomized skin in humans. J Auton Nerv Syst 60: 147–153, 1996

    Google Scholar 

  25. Baron R, Maier C: Reflex sympathetic dystrophy: skin blood flow, sympathetic vasoconstrictor reflexes and pain before and after surgical sympathectomy. Pain 67: 317–326, 1996

    Google Scholar 

  26. Butler SH: Disuse and CRPS. In Harden RN, Baron R, JänigW (eds) Complex regional pain syndrome. Progress in Pain Research and Management. IASP Press, Seattle, 2001, pp 141–150

    Google Scholar 

  27. Daniel CR 3rd, Scher RK: Nail changes secondary to systemic drugs or ingestants. J Am Acad Dermatol 10: 250–258, 1984

    Google Scholar 

  28. Lewis T: Blood Vessels of the Human Skin and Their Responses. Shaw, 1927

  29. LaMotte RH, Lundberg LE, Torebjörk HE: Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. J Physiol (Lond) 448: 749–764, 1992

    Google Scholar 

  30. Holzer P: Peptidergic sensory neurons in the control of vascular functions: mechanisms and significance in the cutaneous and splanchnic vascular beds. Rev Physiol Biochem Pharmacol 121: 49–146, 1992

    Google Scholar 

  31. Ding AH, Porteu F, Sanchez E, Nathan CF: Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science 248: 370–372, 1990

    Google Scholar 

  32. Sorkin LS, XiaoW-H, Wagner R, Myers RR: Tumor necrosis factor-alpha induces ectopic activity in nociceptive primary afferent fibres. Neurosci 81: 255–262, 1997

    Google Scholar 

  33. Bogdan C, Ding A: Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. J Leukoc Biol 52: 119–121, 1992

    Google Scholar 

  34. Green PG, Jänig W, Levine JD: Negative feedback neuroendocrine control of inflammatory response in the rat is dependent on the sympathetic postganglionic neuron. J Neurosci 17: 3234–3238, 1997

    Google Scholar 

  35. Kinnman E, Levine JD: Involvement of the sympathetic postganglionic neuron in capsaicin-induced secondary hyperalgesia in the rat. Neuroscience 65: 283–291, 1995

    Google Scholar 

  36. Schrijvers D, Wanders J, Dirix L, Prove A, Vonck I, van Oosterom A, Kaye S: Coping with toxicities of docetaxel (Taxotere). Ann Oncol 4: 610–611, 1993

    Google Scholar 

  37. Piccart MJ, Klijn J, Paridaens R, Nooij M, Mauriac L, Coleman R, Bontenbal M, Awada A, Selleslags J, Van Vreckem A, Van Glabbeke M: Corticosteroids signifi-cantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer. J Clin Oncol 15: 3149–3155, 1997

    Google Scholar 

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Authors and Affiliations

  1. Klinik für Neurologie, Universitätsklinikum der Christian-Albrechts-Universität zu Kiel, Kiel, Germany

    Gunnar Wasner, Jörn Schattschneider, Andreas Binder & Ralf Baron

  2. Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum der Christian-Albrechts-Universität zu Kiel, Kiel, Germany

    Felix Hilpert & Jacobus Pfisterer

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  1. Gunnar Wasner
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  2. Felix Hilpert
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Wasner, G., Hilpert, F., Schattschneider, J. et al. Docetaxel-induced Nail Changes – A Neurogenic Mechanism: A Case Report. J Neurooncol 58, 167–174 (2002). https://doi.org/10.1023/A:1016002329546

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