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| CASE REPORT |
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| Year : 2015 | Volume
: 1
| Issue : 1 | Page : 30-32 |
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Atypical case of hand foot syndrome due to pegylated liposomal doxorubicin presenting as hyperpigmentation
Manjeet Naresh Ramteke1, Divita Ramesh Bhuraria2, Usha N Khemani1
1 Department of Dermatology, Venereology and Leprosy, Grant Government Medical College and Sir J. J. Group of Hospitals, Mumbai, Maharashtra, India
2 Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India
| Date of Web Publication | 1-Dec-2015 |
Correspondence Address:
Manjeet Naresh Ramteke
Skin OPD No. 19, 1st Floor, OPD Building, G. T. Hospital, L. T. Marg, Dhobi Talao, Mumbai - - 400 001, Maharashtra
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/WKMP-0110.170745
Hand foot syndrome (HFS) or palmar-plantar erythrodysesthesia (PPE) is a relatively frequent and often a serious side effect of anti-cancer drugs including liposomal doxorubicin. Hyperpigmentation as a part of HFS is infrequently reported. A 51-year-old woman on treatment with pegylated liposomal doxorubicin for recurrence of adenocarcinoma of ovary presented with history of itching and burning sensation in her hand and feet. She also noted hyperpigmentation of palms more than soles and discoloration of finger and toe nails. Physical examination revealed diffuse hyperpigmentation of both the palms and soles. This was accompanied by a bluish discoloration of lunulas of finger and toe nails. She was diagnosed with HFS and started on pyridoxine and emollients. The finding of hyperpigmentation noted in our patient is not commonly seen in HFS and believed by many authors to be an initial manifestation of HFS.
Keywords: Hand and foot syndrome, hyperpigmentation, pegylated liposomal doxorubicin
How to cite this article:
Ramteke MN, Bhuraria DR, Khemani UN. Atypical case of hand foot syndrome due to pegylated liposomal doxorubicin presenting as hyperpigmentation. Indian J Drugs Dermatol 2015;1:30-2 |
How to cite this URL:
Ramteke MN, Bhuraria DR, Khemani UN. Atypical case of hand foot syndrome due to pegylated liposomal doxorubicin presenting as hyperpigmentation. Indian J Drugs Dermatol [serial online] 2015 [cited 2023 Jun 1];1:30-2. Available from: https://www.ijdd.in/text.asp?2015/1/1/30/170745 |
| Introduction | |  |
Hand foot syndrome (HFS) or palmar-plantar erythrodysesthesia (PPE) is a relatively frequent and often a serious side effect of anti-cancer drugs such as liposomal doxorubicin, capecitabine, cytarabine, floxuridine, fluorouracil, idarubicin, doxorubicin, sunitinib, sorafenib, pazopanib, vemurafenib, hydroxyurea, mercaptopurine, and cyclophosphamide.[1] Pegylated liposomal doxorubicin (PLD) induces dermal side effects i.e. HFS in up to 80% of cases, probably by its secretion in the sweat onto the skin surface.[2] PLD has been useful as second- or third-line anti-neoplastic agent for the management of platinum-resistant or refractory ovarian carcinoma. The risk for the development of HFS has been reported to be increased by the use of higher concentrations of drug (>50 mg/m 2), treatment courses with relatively short intervals (<4 weeks), and generally seen after a couple of courses of treatment.[3]
| Case Report | | |
A 51-year-old female patient was diagnosed as having adenocarcinoma of ovary (stage 3A) 2 years back. She received chemotherapy with cisplatin 100 mg/m 2 intravenously once every 4 weeks for six cycles. Second-line chemotherapy with PLD (50 mg/m 2 once in every 4 weeks) was started in view of recurrence of the disease over the last 5 months. Ten days after the third cycle, the patient developed itching and burning sensation on bilateral hands and feet. This was associated with dark colored pigmentation, dryness, and scaling. She also had discoloration of finger and toe nails. Physical examination revealed diffuse hyperpigmentation of both the palms and dorsa of hands [Figure 1] and dorsa of toes. There was desquamation around the toes and over bilateral palms along with bluish discoloration of the lunulae of nails [Figure 2] and [Figure 3]. There were no other significant nail changes. No hyperpigmentation was observed in the mucosa or elsewhere. Histopathology showed hyperkeratosis, mild spongiosis, hypergranulosis in epidermis and edema, and sparse perivascular lymphocytic infiltrate in superficial dermis [Figure 4]. The patient was prescribed topical steroid, emollient, and oral pyridoxine 100 mg daily, and the drugs were continued. | Figure 2: Hyperpigmentation with dryness and scaling mostly on the knuckles with bluish discoloration of the lunulae of all finger nails.
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 | Figure 3: Hyperpigmentation and desquamation around the toes with bluish discoloration of lunula.
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 | Figure 4: Mild spongiosis, hypergranulosis in epidermis, and sparse perivascular lymphocytic infiltrate in the superficial dermis.
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| Discussion | | |
HFS was first reported in 1974 by Zuelke, with mitotane therapy.[4] HFS is a common adverse effect associated with liposomal doxorubicin. The exact pathogenesis of HFS is not known, but it has been suggested that following local trauma associated with routine activities, PLD may extravasate from the deeper micro-capillaries of the hands and feet and penetrate into the stratum corneum leading to a local inflammatory tissue reaction.[5] It is characterized by painful, red macular and/or papular bullous skin eruptions. HFS has been classified into four grades in which Grade 1 shows only slight dysesthesia and mild redness in lateral aspect of fingers and toes, Grade 2 shows dysesthesia but no pain and severe redness and/or swelling not affecting daily activity, Grade 3 shows dysesthesia with pain and severe redness and/or swelling affecting daily activity, and Grade 4 shows severe pain, desquamation, blistering, and ulceration impairing function in daily activities.[6] Hyperpigmentation with scaling, as seen in our patient, is not included in the grading system, making it a case of atypical HFS.
Many authors believe that hyperpigmentation of hand and foot instead of erythema may be a part of HFS and can occur as an initial manifestation in Grade 1.[1],[7] Pigmentation of the tongue and buccal mucosa, localized pigmentation of the palms, soles, and axillae as well as pigmentation along palmar or digital creases has been reported with the use of doxorubicin. Many workers have reported that the administration of the doxorubicin caused dark pigmentation of nails including pigmented nail bands.[8] The mechanism of action which has been described is direct stimulation of melanogenesis in the melanocytes by melanocyte stimulating hormone and adrenocorticotrophic hormone.[9] Other variations
of HFS include scleroderma-like changes, keratoderma-like thickening, longitudinal melanonychia, and paronychia.[10]
Histopathology findings of HFS are nonspecific and include mild spongiosis, scattered necrotic and dyskeratotic keratinocytes, and hydropic degeneration of the basal layer. Dermal changes in most cases include dilated blood vessels, papillary edema, and a sparse superficial perivascular lymphohistiocytic infiltrate.[3]
Management of HFS is often palliative and includes topical emollient, antibiotics to prevent secondary infection, topical steroid, Vitamin B6, and discontinuation of the offending drug in severe cases.[11] As PLD was essential for the treatment of malignancy and adverse drug reaction was not very severe, it was continued in our patient. The results of the observation by Lademann et al. demonstrated that topical application of the ointment containing antioxidants with a high radical protection factor is an efficient strategy against the development of HFS during chemotherapy with PLD.[2]
Pigmentation and scaling as a variation of PPE due to PLD was an unusual feature in our case which should be kept in mind when such anti-cancer are prescribed for the treatment of advanced malignancies.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
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