• Users Online: 752
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2015  |  Volume : 1  |  Issue : 1  |  Page : 30-32

Atypical case of hand foot syndrome due to pegylated liposomal doxorubicin presenting as hyperpigmentation

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 Publication1-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
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/WKMP-0110.170745

Rights and Permissions

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 Top

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 Top

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 1: Hyperpigmentation with dryness and scaling of both the palms.

Click here to view
Figure 2: Hyperpigmentation with dryness and scaling mostly on the knuckles with bluish discoloration of the lunulae of all finger nails.

Click here to view
Figure 3: Hyperpigmentation and desquamation around the toes with bluish discoloration of lunula.

Click here to view
Figure 4: Mild spongiosis, hypergranulosis in epidermis, and sparse perivascular lymphocytic infiltrate in the superficial dermis.

Click here to view

  Discussion Top

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


Conflicts of interest

There are no conflicts of interest.

  References Top

Sanghi S, Grewal RS, Vasudevan B, Nagure A. Capecitabine induced Hand-Foot Syndrome: Report of two cases. Med J Armed Forces India 2013;69:65-7.  Back to cited text no. 1
Lademann J, Martschick A, Kluschke F, Richter H, Fluhr JW, Patzelt A, et al. Efficient prevention strategy against the development of a palmar-plantar erythrodysesthesia during chemotherapy. Skin Pharmacol Physiol 2014;27:66-70.  Back to cited text no. 2
Çakıl B, Serdengeçti S, Uçar FG. Liposomal doxorubicin induced severe palmar-plantar erythrodysesthesia. J Turk Acad Dermatol 2007;1:71402.  Back to cited text no. 3
Mangana J, Zipser MC, Conrad C, Oberholzer PA, Cozzio A, Knuth A, et al. Skin problems associated with pegylated liposomal doxorubicin-more than palmoplantar erythrodysesthesia syndrome. Eur J Dermatol 2008;18:566-70.  Back to cited text no. 4
Lorusso D, Di Stefano A, Carone V, Fagotti A, Pisconti S, Scambia G. Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome). Ann Oncol 2007;18:1159-64.  Back to cited text no. 5
von Moos R, Thuerlimann BJ, Aapro M, Rayson D, Harrold K, Sehouli J, et al. Pegylated liposomal doxorubicin-associated hand-foot syndrome: Recommendations of an international panel of experts. Eur J Cancer 2008;44:781-90.  Back to cited text no. 6
Vasudevan B. Hyperpigmentation due to capecitabine. Indian J Pharmacol 2010;42:326-8.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
Vimala AM. Enhanced toxicity potential of a regimen on addition of doxorubicin in combination chemo-therapy. Indian J Dermatol Venereol Leprol 1997;63:347-53.  Back to cited text no. 8
[PUBMED]  Medknow Journal  
Vázquez-Bayo C, Rodríguez-Bujaldón AL, Jiménez-Puya R, Galán-Gutiérrez M, Moreno-Giménez JC. Capecitabine-induced hyperpigmentation. Actas Dermosifiliogr 2007;98:491-3.  Back to cited text no. 9
Narasimhan P, Narasimhan S, Hitti IF, Rachita M. Serious hand-and-foot syndrome in black patients treated with capecitabine: Report of 3 cases and review of the literature. Cutis 2004;73:101-6.  Back to cited text no. 10
Surjushe A, Vasani R, Medhekar S, Thakre M, Saple DG. Hand-foot syndrome due to capecitabine. Indian J Dermatol 2008;53:43-4.  Back to cited text no. 11
[PUBMED]  Medknow Journal  


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Case Report
Article Figures

 Article Access Statistics
    PDF Downloaded71    
    Comments [Add]    

Recommend this journal