|Year : 2020 | Volume
| Issue : 2 | Page : 88-92
Nail manifestations in cancer chemotherapy: A cross-sectional study
Zainaba Mizaj1, Spandana P Hegde2, Guruprasad Bhat3, Vishal B Amin2, Malcolm Pinto2, Manjunath M Shenoy2
1 Department of Dermatology, Aster Medcity, Kochi, Kerala, India
2 Department of Dermatology, Venereology and Leprosy, Yenepoya Medical College, Mangalore, Karnataka, India
3 Department of Medical Oncology, Yenepoya Medical College, Mangalore, Karnataka, India
|Date of Submission||16-Jul-2020|
|Date of Acceptance||25-Aug-2020|
|Date of Web Publication||10-Nov-2020|
Dr. Spandana P Hegde
Department of Dermatology, Venereology and Leprosy, Yenepoya Medical College Hospital, Mangalore - 575 018, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Anticancer chemotherapy is associated with multisystem adverse effects. Chemotherapy can affect skin, nails, and hair and may sometimes affect the quality of life to the point of requiring discontinuation of therapy. There are many new chemotherapeutic agents, and with that, a rise in the adverse effects attributed to them. Purpose: To evaluate the frequency of nail changes occurring due to anticancer therapy. Methods: We screened 100 cancer patients admitted in the oncology ward of a tertiary care center in South India from July to September 2017. The nail changes were documented and analyzed with emphasis on developing a relationship if any with a chemotherapeutic agent. Results: Nail changes were observed in 62 (62%) cases. Breast carcinoma (20 cases) was the most common malignancy. Doxorubicin (36 cases) and cyclophosphamide (27 cases) were the most common chemotherapeutic drugs associated with nail changes. Pigmentary changes (32 cases) were the most common nail plate changes. Blue lunula (24 cases) was the most common nail bed change, occurring with cyclophosphamide/doxorubicin. Pyogenic granuloma was the only nail fold change that was noted in a patient of carcinoma of breast treated with gefitinib. Conclusion: Cancer chemotherapy may be associated with a variety of nail changes. Addressing nail changes may have the potential to improve cancer treatment patients' quality of life.
Keywords: Blue lunula, chemotherapy, melanonychia, nail
|How to cite this article:|
Mizaj Z, Hegde SP, Bhat G, Amin VB, Pinto M, Shenoy MM. Nail manifestations in cancer chemotherapy: A cross-sectional study. J Dermatol Dermatol Surg 2020;24:88-92
|How to cite this URL:|
Mizaj Z, Hegde SP, Bhat G, Amin VB, Pinto M, Shenoy MM. Nail manifestations in cancer chemotherapy: A cross-sectional study. J Dermatol Dermatol Surg [serial online] 2020 [cited 2021 Apr 23];24:88-92. Available from: https://www.jddsjournal.org/text.asp?2020/24/2/88/300400
| Introduction|| |
Systemic chemotherapy can be considered as an important treatment modality for a number of neoplastic diseases. This in turn can result in a variety of skin and nail changes as adverse effects. A myriad of nail changes may be seen in patients on systemic chemotherapy, with chemotherapeutic agents being the most frequent cause of drug-induced nail changes. These changes may be limited to a single nail or multiple nails. Chemotherapy-induced nail changes are usually asymptomatic and resolve with the cessation of the same. Even though they may not be a threat to the patient's life, these nail changes can be cosmetically very distressing. They may be associated with pain and discomfort, thereby impairing activities of daily living and affecting the quality of life. Most of the drug-induced nail changes are seen secondary to acute toxicity to the nail epithelium, with the symptoms differing depending on the component of nail affected and the severity of insult.,
We conducted a prospective observational study to evaluate the pattern of nail changes occurring in patients due to anticancer therapy and to determine their frequency.
| Methods|| |
This was a cross-sectional study conducted at a tertiary care center in South India. The study was registered with the institutional review board, and approval was taken from the institutional ethics committee. A total of 100 cancer patients on chemotherapy admitted under the department of medical oncology from July 2017 to September 2017 were screened. Patients who developed nail changes after initiation of chemotherapy were included in the study. We excluded patients who had nail manifestations secondary to other dermatological and systemic conditions, patients with a history of local nail disease, and those with occupational contact with chemicals that could induce nail changes.
Detailed history was obtained from all the patients. The parameters recorded focused on demographic details, associated malignancy, other illnesses, and details of chemotherapy such as drugs used, dosage, and cycles. The duration of onset of nail changes was noted. They were then subjected to relevant clinical examination which included general, systemic, and dermatological examination. The nail changes were described and recorded with necessary photographic documentation. Potassium hydroxide mount of the nail was done to rule out any coexistent onychomycosis in suspected cases.
Descriptive statistics such as mean ± standard deviation (SD) and median were calculated. The prevalence of various nail changes of anticancer chemotherapy was expressed as percentages.
| Results|| |
Among 100 consecutive patients undergoing cancer chemotherapy, 62 patients (62%) had nail changes [Table 1]. The study population included patients aged 4–68 years (mean age ± SD: 43.9 ± 16.8). The male:female ratio was 1:2.5. The most common malignancy among the patients with nail changes was breast carcinoma (32.2%) followed by Hodgkin's lymphoma (11.3%) and colon cancer [9.7%, [Figure 1]. Doxorubicin (58%) and cyclophosphamide (43.5%) were noted to be the most common anticancer chemotherapeutic drugs used. Combination chemotherapy was used in 95.1% of cases [Figure 2]. The duration of the incubation period from the initial administration of the chemotherapeutic agent to the clinical appearance of nail changes varied from 3 to 8 weeks, with a median of 6 weeks. Finger nail changes were noted in all patients, and toe nail changes were seen in 13 (20.9%) patients.
|Table 1: Our findings and findings from previous studies in relation to nail changes and their association with various anticancer chemotherapeutic drugs and diseases|
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|Figure 1: Malignancies noted in the study of nail manifestations in cancer chemotherapy. Ca: Carcinoma, CML: Chronic myeloid leukemia, CLL: Chronic lymphocytic leukemia, ALL: Acute lymphoblastic leukemia, HL: Hodgkin's lymphoma, NHL: Non-Hodgkin's lymphoma, MFH: Malignant fibrous histiocytoma|
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|Figure 2: Anticancer chemotherapeutic drugs associated with nail changes|
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The nail changes were classified based on the involvement of the nail plate, nail bed, and nail folds [Table 1]. The nail component affected most commonly following various chemotherapy was the nail plate (54.8%), followed by nail bed (43.5%) and nail fold (1.6%). The most common nail changes were blue lunula (38.7%) and longitudinal melanonychia (27.4%).
Pigmentary changes were noted to be the most common (32 cases) among the various nail plate changes studied which included longitudinal, transverse [Figure 3]a, and diffuse melanonychia [Figure 3]b. Mees' lines were seen in two cases.
|Figure 3: (a) Transverse melanonychia in a patient of carcinoma breast on docetaxel. (b) Diffuse melanonychia in a patient of Hodgkin's lymphoma on doxorubicin/bleomycin/vinblastine|
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Nail bed changes included blue lunula [Figure 4]a (24 cases), Muehrcke's lines [Figure 4]b (2 cases), and half and half nails [Table 1] and [Figure 5]a (1 case). Pyogenic granuloma [Figure 5]b was the only nail fold change that was reported in a patient of carcinoma of breast who was treated with epidermal growth factor receptor (EGFR) inhibitor, gefitinib.
|Figure 4: (a) Blue lunula in a patient of breast carcinoma on doxorubicin/cyclophosphamide. (b) Muehrcke's lines in a patient of Ewing's sarcoma on vincristine/cyclophosphamide|
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|Figure 5: (a) Half and half nails in a patient of non-Hodgkin's lymphoma on doxorubicin/cyclophosphamide. (b) Pyogenic granuloma in a patient of carcinoma breast on Gefitinib|
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| Discussion|| |
Chemotherapeutic agents usually affect the rapidly growing cells, thereby making the skin, hair follicles, and nail matrix, frequent targets of their associated toxicities. Chemotherapeutic agents were the most common cause of drug-induced nail changes. The majority of previous studies have described the mucocutaneous adverse effects of cancer chemotherapy.,, Our study specifically aimed at studying only the nail manifestations in patients on anticancer chemotherapy. There is a paucity of studies describing exclusively the nail changes in chemotherapy recipients. Nail changes were the most common mucocutaneous adverse effects of cancer chemotherapy as observed by Pavey et al. and Naveed et al. In our study, nail changes associated with chemotherapy were noted in 62% of cases, which was comparable to other studies., However, Naveed et al. observed a higher frequency of nail changes (85.8%).
Depending on the component of the nail affected, the nail changes may be categorized into those that involve the nail plate, the nail bed, or the nail folds. Nail changes following chemotherapy may involve the nail matrix, causing aberrations in growth of the nail plate (Mees' lines, Beau's lines, onychomadesis, and melanonychia) while those secondary to insults to the nail bed result in abnormalities such as Muehrcke's lines, onycholysis, subungual hemorrhage, or hematoma. On the other hand, if the affected nail component is the proximal nail fold, changes seen include paronychia and periungual pyogenic granuloma.,
Melanonychia was the most common manifestation seen in our study in 51.6% of cases. Previous studies have documented nail discoloration in 70%–81% of cases on chemotherapy.,,
The lower prevalence of melanonychia in our study may be attributed to the documentation of melanonychia as a nail plate alteration and bluish discoloration of the lunula as a distinct entity in the nail bed. Melanonychia occurs in three forms: longitudinal, transverse, and diffuse. Chemotherapeutic agents stimulate normally quiescent nail matrix melanocytes resulting in nail plate pigmentation and hampered nail growth.
In our study, longitudinal pigmentary bands were the most common pigmentary change occurring in 53.1% of cases, including in patients who were on platins, 5-fluorouracil (5-FU), cyclophosphamide, etoposide, epirubicin, capecitabine, gemcitabine, and cytarabine. Diffuse melanonychia was most commonly seen following the use of doxorubicin, bleomycin, vinblastine, paclitaxel and carboplatin, which was similar to previous results. A breast cancer patient on docetaxel monotherapy developed transverse melanonychia. Transverse melanonychia was also seen in patients following treatment with vincristine, daunorubicin, gemcitabine, cytarabine, and methotrexate in our study. Similar results were seen in studies conducted by Naveed et al.
Mees' lines occurred in 2 patients treated with cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP regimen) and cyclophosphamide/vincristine/doxorubicin/cytarabine. Mees' lines have been reported by previous studies with the above drug combinations.,,, A Mees' line is a solitary, white, nonblanchable transverse band in the nail plate due to sudden toxic damage to the nail matrix. This leads to faulty keratinization which causes altered light diffraction in the retained parakeratotic onychocytes. It is seen to parallel the lunula. A nail plate may contain a single or multiple Mees' lines. Involvement of multiple nails may give a clue to the presence of an underlying systemic disease.
Blue lunula was the most common nail bed change that occurred in 38.7% of our patients. In contrary, blue lunula has been infrequently reported by other studies. This may be due to counting it as a form of melanonychia or nail discoloration in previous studies, whereas we categorized it into a distinct nail bed change. We observed blue lunula following administration of doxorubicin and cyclophosphamide as well as ifosfamide, 5-FU, capecitabine, and platin. Blue chromonychia has been reported in patients receiving chemotherapeutic agents such as doxorubicin, cyclophosphamide, and bleomycin cocktail therapy because of activation of matrix melanocytes.
In our study, Muehrcke's lines were seen in two (3.2%) patients receiving vincristine/cyclophosphamide and cisplatin/5-FU/docetaxel. Saraswat et al. also observed Muehrcke's lines in 3.2% of cases. Chen et al. reported Muehrcke's lines to be the most common nail change in their study of nail changes in pediatric population . Muehrcke's lines are blanchable, paired, white lines that appear secondary to vascular congestion in the nail bed. These lines appear parallel to the contour of the lunula, due to the involvement of the nail bed.
We observed half and half nails in one patient on doxorubicin/cyclophosphamide. They have been rarely reported in patients receiving anticancer chemotherapeutic agents. Half and half nails are characterized by a white zone in the proximal part and a brownish zone in the distal aspect (20%–60%) with a sharp demarcation. Although the exact pathogenesis remains unclear, the primary pathology appears to be in the nail bed. The reddish distal band leads to the constricting venous return in the nail bed.
In our study, one patient developed periungual pyogenic granuloma of the index finger due to EGFR inhibitor, gefitinib. Periungual pyogenic granuloma occurs due to overgrowth of granulation tissue. The exact pathogenesis is uncertain, but it is implicated that the drug may lead to activation of angiogenic factors, leading to the development of painful bleeding nodules in the proximal and lateral nail folds. The great toe and thumb are the most frequently affected, although any digit may be involved.
[Table 1] summarizes our findings and findings from previous studies in relation to nail changes and their association with various anticancer chemotherapeutic drugs and diseases.,,,,,,,,,,,,
The limitations of our study were a modest size and inability to establish a causal association between the type of nail change and a chemotherapeutic drug as majority of our patients were on combination chemotherapy.
| Conclusion|| |
Cancer chemotherapy may be associated with a myriad of nail changes. Unnecessary testing and use of ineffective wasteful treatment may be prevented by raising the awareness of anticancer drug-induced nail changes. Undue anxiety about the same may affect the continuation of chemotherapy and effective treatment of patients. Awareness among dermatologists and oncologists of these nail changes and their associated drugs can aid in arriving at an early diagnosis thereby avoiding inadvertent measures.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Hinds G, Thomas VD. Malignancy and cancer treatment-related hair and nail changes. Dermatol Clin 2008;26:59-68, viii.
Gupta A, Parakh A, Dubey AP. Chemotherapy induced nail changes. Indian J Dermatol 2008;53:204-5.
] [Full text]
Gilbar P, Hain A, Peereboom VM. Nail toxicity induced by cancer chemotherapy. J Oncol Pharm Pract 2009;15:143-55.
Piraccini BM, Tosti A. Drug-induced nail disorders: incidence, management and prognosis. Drug Saf 1999;21:187-201.
Kamil N, Kamil S, Ahmed SP, Ashraf R, Khurram M, Ali MO. Toxic effects of multiple anticancer drugs on skin. Pak J Pharm Sci 2010;23:7-14.
Pavey RA, Kambil SM, Bhat RM. Dermatological adverse reactions to cancer chemotherapy. Indian J Dermatol Venerol Leprol 2015;81:434.
Naveed S, Thappa DM, Dubashi B, Pandjatcharam J, Munisamy M, Singh N. Mucocutaneous adverse reactions of cancer chemotherapy and chemoradiation. Indian J Dermatol 2019;64:122-8.
] [Full text]
Menon A, Handattu S, Shetty J, Girisha BS. Study of cutaneous adverse effects of cancer chemotherapy. Clin Dermatol Rev 2018;2:19-24. [Full text]
Saraswat N, Sood A, Verma R, Kumar D, Kumar S. Nail changes induced by chemotherapeutic agents. Indian J Dermatol 2020;65:193-8. [Full text]
Chen W, Yu YS, Liu YH, Sheen JM, Hsiao CC. Nail changes associated with chemotherapy in children. J Eur Acad Dermatol Venereol 2007;21:186-90.
Woo IS, Shim KH, Kim GY, Lee MA, Kang JH, Hong YS, et al
. Nail changes during docetaxel containing combination chemotherapy. Korean J Intern Med 2004;19:132-3.
Anoun S, Qachouh M, Lamchahab M, Quessar A, Benchekroun S. Mees' lines in an acute myeloid leukemia patient. Turk J Haematol 2013;30:340.
Mendiratta V, Jain A. Nail dyschromias. Indian J Dermatol Venereol Leprol 2011;77:652-8.
] [Full text]
Afsar FS, Ozek G, Vergin C. Half-and-half nails in a pediatric patient after chemotherapy. Cutan Ocul Toxicol 2015;34:350-1.
Piraccini BM, Iorizzo M, Tosti A. Drug-induced nail abnormalities. Am J Clin Dermatol 2003;4:31-7.
Ferreira MN, Ramseier JY, Leventhal JS. Dermatologic conditions in women receiving systemic cancer therapy. Int J Womens Dermatol 2019;5:285-307.
Dasanu CA, Vaillant JG, Alexandrescu DT. Distinct patterns of chromonychia, Beau's lines, and melanoderma seen with vincristine, adriamycin, dexamethasone therapy for multiple myeloma. Dermatol Online J 2006;12:10.
Hong J, Park SH, Choi SJ, Lee SH, Lee KC, Lee JI, et al
. Nail toxicity after treatment with docetaxel: A prospective analysis in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol 2007;37:424-8.
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