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CORRESPONDENCE |
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| Year : 2022 | Volume
: 67
| Issue : 6 | Page : 779-781 |
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| Irinotecan-induced serpentine supravenous hyper-pigmentation |
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Vishal Gaurav1, Archana Singal2
1 From the Department of Dermatology and Venereology, All India Institute of Medical Sciences, New Delhi, Delhi, India
2 Department of Dermatology and STD, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi, India
| Date of Web Publication | 23-Feb-2023 |
Correspondence Address:
Archana Singal
Department of Dermatology and STD, University College of Medical Sciences and Guru Teg Bahadur Hospital, Dilshad Garden, Delhi
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijd.ijd_397_22
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How to cite this article:
Gaurav V, Singal A. Irinotecan-induced serpentine supravenous hyper-pigmentation. Indian J Dermatol 2022;67:779-81 |
Sir,
Cancer chemotherapy-associated dyspigmentation is a well-recognized but under-reported entity. Various anti-neoplastic agents have been implicated in the causation of both hyper-melanosis and hypomelanosis. Different patterns of dyspigmentation, especially hyper-pigmentation involving the skin, mucous membranes, and nails, have been described in the literature.[1]
Serpentine supravenous hyper-pigmentation (SSH) is characterized by hyper-pigmentation of skin along the superficial veins. SSH may occur following intravenous drug abuse or because of intravenous administration of anti-cancer agents.[2] However, to the best of our knowledge, SSH following irinotecan chemotherapy has not been reported previously.
A 23-year-old female presented with asymptomatic bizarre-shaped pigmentation over the right forearm and left leg. She was diagnosed with ovarian primary mucinous adenocarcinoma with perihepatic, serosal, and pulmonary metastasis 4 years back and received three cycles of neo-adjuvant chemotherapy with carboplatin and paclitaxel, followed by cyto-reductive surgery and four cycles thereafter. Following this, she was in remission for 2 years before developing recurrence of metastatic perihepatic, serosal, and pulmonary deposits. She was given six cycles of carboplatin and paclitaxel chemotherapy without any significant improvement. The regimen was changed to three cycles of gemcitabine and doxorubicin, 30 days apart with poor response. Further on, she received three cycles of irinotecan chemotherapy, of which the first and second cycles were delivered intravenously through the proximal and distal right dorsal forearm and the third through the left leg. The patient presented for dermatology consultation after 3 weeks following third cycle of irinotecan chemotherapy. Cutaneous examination revealed linear and serpiginous hyper-pigmentation overlying the superficial veins originating from the points of prior intravenous access in the right forearm [Figure 1]a and left leg [Figure 1]b on a background of dry skin. There was neither evidence of nail, mucosal, or generalized skin hyper-pigmentation nor any evidence of extravasation or phlebitis. The patient was counselled regarding the benign and self-resolving nature of the lesions. | Figure 1: Linear and serpiginous hyper-pigmentation overlying the superficial veins, originating from the points of intravenous access in (a) right forearm and (b) left leg
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Irinotecan is an S-phase-specific pyranoindolizinoquinoline, derived semi-synthetically from camptothecin, a plant-based alkaloid. It stabilizes the cleavable complex (a catalytic intermediate formed between topoisomerase I and DNA) preventing re-ligation of DNA strand breaks, thus inhibiting DNA replication leading to apoptosis because of inability to repair the defect. It is used for colorectal, ovarian, and non-small-cell lung cancer.[3] Cutaneous adverse effects following irinotecan chemotherapy are rare and include alopecia, xerosis cutis, and localized acral hyper-pigmentation of skin, mucosa, and nails.[4],[5]
SSH was first described by Hrushesky in 1976 following administration of fluorouracil for metastatic prostate cancer.[6] The implicated anti-neoplastic drugs are enlisted in [Table 1].[2],[7],[8] Although paclitaxel, carboplatin, and doxorubicin are known to cause SSH, the time lag between their administration and development of SSH and the temporal association with irinotecan administration favor the latter as the most likely agent in this case. The possibility of an augmented or delayed reaction to any or combination of these drugs cannot be ruled out as SSH has been reported to occur as late as the 18th chemotherapy cycle.[9] The pigmentation usually persists for months with gradual fading. The clinical differential diagnosis includes thrombophlebitis, erythema ab igne, and livedo reticularis. Thrombophlebitis lesions are erythematous and appear like ascending tender cord-like structures on palpation. Livedo reticularis and erythema ab igne, both present as transient mottled/reticular discoloration, occuring on exposure to cold and heat, respectively.
The pathophysiology is incompletely understood, and many hypotheses have been put forth, including direct stimulation of tyrosinase or indirect stimulation by depletion of reduced thioredoxin (tyrosinase inhibitors) and thermal injury to melanocytes. The most favored is direct cytotoxicity of the agent following extravasation because of a focally necrotic endothelium on basal keratinocytes and melanocytes leading to apoptosis, inflammation, and subsequent hyper-pigmentation.[2],[7],[8] The treatment is often unnecessary and disappointing. Prophylactic measures include venous saline washing following each infusion, slow infusion, and rotation of site of intravenous access.[7]
We are reporting this relatively uncommon cutaneous side effect of chemotherapy to sensitize the physicians about its occurrence.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
 References | |  |
| 1. | Pavey RA, Kambil SM, Bhat RM. Dermatological adverse reactions to cancer chemotherapy. Indian J Dermatol Venereol Leprol 2015;81:434-43.  [ PUBMED] [Full text] |
| 2. | Akyurek FT, Sari N, Ugurluoglu C, Kurtipek GS. Serpentine supravenous hyperpigmentation related to carboplatin and vinorelbine chemotherapy: A case report. Dermatol Ther 2019;32:12981. doi: 10.1111/dth. 12981. |
| 3. | PubChem. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004. PubChem Compound Summary for CID 60838, Irinotecan. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Irinotecan [Last accessed on 2021 Aug 20]. |
| 4. | Nakanishi K, Goto K, Kondo K, Hiramoto K, Ooi K. Irinotecan-induced skin dryness is ameliorated by orally administered high-dose vitamin C in mice. J Exp Pharmacol 2019;11:109-14. |
| 5. | Nestor LA, Flint S, Galvin S. Unusual case of hyperpigmentation secondary to irinotecan. BMJ Case Rep 2016;2016:2016217545. doi: 10.1136/bcr-2016-217545. |
| 6. | Hrushesky WJ. Letter: Serpentine supravenous fluorouracil hyperpigmentation. JAMA 1976;236:138. |
| 7. | Geddes ER, Cohen PR. Antineoplastic agent-associated serpentine supravenous hyperpigmentation: Superficial venous system hyperpigmentation following intravenous chemotherapy. South Med J 2010;103:231-5. |
| 8. | Noori M, Hunter-Ellul L, Kelly B. Serpentine supravenous hyperpigmentation following cisplatin and pemetrexed chemotherapy. Cutis 2017;99:20-2. |
| 9. | Hrushesky WJ. Unusual pigmentary changes associated with 5-fluorouracil therapy. Cutis 1980;26:181-2. |
[Figure 1]
[Table 1] |
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