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ISSN: Print -2349-0977, Online - 2349-4387


 
 Table of Contents  
ORIGINAL CONTRIBUTION - DERMATOLOGY CLINICS IN PEDIATRIC HEMATO ONCOLOGY
Year : 2016  |  Volume : 3  |  Issue : 2  |  Page : 74-77

Mucocutaneous manifestations in patients on chemotherapy with pediatric hematological malignancies


1 Department of Dermatology and S.T.D., Lady Hardinge Medical College and Associated Hospitals, New Delhi, India
2 Department of Pediatrics, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India

Date of Web Publication30-Dec-2016

Correspondence Address:
Taru Garg
Department of Dermatology and S.T.D., Lady Hardinge Medical College and Associated Hospitals, New Delhi - 110 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2349-0977.197209

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  Abstract 

Introduction: A wide variety of chemotherapeutic agents are currently in use for the treatment of hematological malignancies in children. A spectrum of mucocutaneous adverse effects has been attributed to these agents, however, the data largely consists of case reports and case series. Material and Methods: Proforma of all pediatric patients up to 18 years of age, with confirmed hematological malignancies (lymphoma and leukemia), undergoing chemotherapy, and attending the pediatric hemato-oncology clinic of a tertiary care hospital over a period of 2 years were analyzed. A detailed history, mucocutaneous examination and investigations were recorded as per  the proforma. The results are presented as mean ± standard deviation. The prevalence of various side effects of chemotherapy is presented as percentages. Results: The age of the patients ranged from 1.2 to 14 years (mean age: 6.6 ± 3.2 years). The duration of the disease ranged from 2 to 122 weeks. Mean duration of chemotherapy was 23.9 ± 24.7 weeks. The analysis consisted of 38 (76%) males and 12 (24%) females (M: F: 3.2:1). Seventy-four percent of the patients had B-cell acute lymphoblastic leukemia (ALL), 6 patients had T-cell ALL, 3 patients had Philadelphia chromosome (+) T-cell ALL, 3 patients had non-Hodgkins lymphoma (NHL) and one patient had hemophagocytic lymphohistiocytosis (HLH). Methotrexate (72%) was the most common agent used followed by vincristine (68%), 6-mercaptopurine (58%), daunomycin (48%), and asparaginase (30%). Hyper-pigmentation was the most common cutaneous side effect noticed in 6 patients. Three patients developed abscess. Two patients each developed tinea corporis, petechie, and thrombophlebitis. One patient each had scabies, pityriasis versicolor, miliaria rubra, allergic contact dermatitis, lip lick cheilitis, ear discharge, and conjunctivitis. One patient developed acute methotrexate toxicity. A total of 24 patients developed mucosal lesions, with aphthous ulcer (20%) being the most common, followed by oral candidiasis (12%) and herpes labialis (12%). Seventeen (34%) patients had diffuse anagen effluvium. Most common change affecting the nails among the study patients was Beau's lines for both fingernails (26%) and toenails (36%). Other less common changes included melanonychia, leuconychia, Mees lines, Muehrcke's nails, half and half nails, etc. Conclusion: The mucocutaneous manifestations associated with chemotherapy cause significant morbidity and possibly mortality in children. A proper knowledge of these manifestations can help in early identification and withdrawal of the offending agents and preventing the morbidity with appropriate and timely management.

Keywords: Chemotherapy, hematological malignancy, malignancy


How to cite this article:
Garg T, Sanke S, Yadav P, Chander R, Chandra J, Mittal S. Mucocutaneous manifestations in patients on chemotherapy with pediatric hematological malignancies. Astrocyte 2016;3:74-7

How to cite this URL:
Garg T, Sanke S, Yadav P, Chander R, Chandra J, Mittal S. Mucocutaneous manifestations in patients on chemotherapy with pediatric hematological malignancies. Astrocyte [serial online] 2016 [cited 2017 Feb 26];3:74-7. Available from: http://www.astrocyte.in/text.asp?2016/3/2/74/197209


  Introduction Top


A wide variety of chemotherapeutic agents are currently in use for the treatment of hematological malignancies in children. A spectrum of mucocutaneous adverse effects has been attributed to these agents, however, the data largely consists of case reports and case series. [1],[2] Only a few available studies throw light on the cutaneous manifestations caused by chemotherapy in children with hematological malignancies. [3] Hence, we planned to analyze the spectrum of adverse effects caused by these agents on skin, mucosa, and appendages.


  Materials and Methods Top


This was a retrospective analysis of records, done over a period of 2 years (2013-2014). Proforma of all the patients attending the pediatric hemato-oncology clinic of Kalawati Saran Hospital were analyzed. All pediatric patients with confirmed hematological malignancies (lymphoma and leukemia), undergoing chemotherapy, and up to 18 years of age, who had muco-cutaneous manifestations were included in the analysis.

A detailed history, mucocutaneous examination and investigations (including grams stain, zeihl nelson stain, potassium hydroxide mount and cultures for bacteria/fungi) were recorded as per proforma.

Statistical analysis

The results were written as mean ± standard deviation. The prevalence of various side effects of chemotherapy is presented as percentages.


  Results Top


The age of patients ranged from 1.2 to 14 years (Mean age: 6.6 ± 3.2 years). The duration of disease ranged from 2 to 122 weeks. Mean duration of chemotherapy was 23.9 ± 24.7 weeks.

The study consisted of 38 (76%) males and 12 (24%) females. (M: F = 3.2:1). Seventy-four percent patients had B-cell acute lymphoblastic leukemia (ALL), 6 patients had T-cell ALL, 3 patients had Philadelphia chromosome (+) T-cell ALL, 3 patients had non-Hodgkins lymphoma (NHL), and 1 patient had haemophagocytic lymphohistiocytosis (HLH). Twenty-seven patients (54%) belonged to high risk ALL, whereas 23 patients (46%) to standard risk ALL [Table 1].
Table 1: Diagnosis of Study Patients


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Type of chemotherapy agent

Methotrexate (72%) was the most common agent used followed by vincristine (68%), 6-mercaptopurine (58%), daunomycin (48%), and asparaginase (30%) [Table 2].
Table 2: Type of Chemotherapeutic Agent Used in the Study Patients


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Adverse effects of chemotherapy is presented in [Figure 1].
Figure 1: Graph showing adverse effects of chemotherapy in study patients

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Cutaneous changes

Hyperpigmentation


Hyperpigmentation was the most common cutaneous side effect noticed in 6 study patients. Two patients had hyperpigmentation of knuckles and bilateral palms (both were on Vincristine, 6-mercaptopurine and Methotrexate). Two patients had hyperpigmentation of knuckles only (one was on 6-mercaptopurine and methotrexate and one on allopurinol and vincristine). Two patients had diffuse hyperpigmentation of the skin.

Infections

Three patients developed abscess (one at the site of lumbar puncture, one perianal, and one gluteal). Two patients developed tinea, 1 patient each had scabies and pityriasis versicolor. One patient each had ear discharge and conjunctivitis.

Others

One patient developed acute methotrexate toxicity. Two patients developed petechie, 1 miliaria rubra, and 2 patients had thrombophlebitis following cannulation. One patient developed allergic contact dermatitis and 1 had lip lick cheilitis.

Mucosal changes

A total of 24 patients developed mucosal lesions, with aphthous ulcer (20%) being the most common, followed by oral candidiasis (12%) and herpes labialis (12%) [Table 3] and [Figure 2].
Figure 2: Graph showing mucosal changes among the study patients

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Table 3: Mucosal Changes in the Study Patients


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Hair changes

Seventeen (34%) patients had diffuse anagen effluvium. Thirty-three patients did not have any complaints related to the hair.

Nail changes

Most common change affecting the nails among the study patients was Beau's lines for both fingernail (26%) and toenail (36%). Forty-eight percent did not have any change in their fingernails, and 50% patients did not have any pathology in the toenails. Other less common changes included melanonychia, leuconychia, Mees lines, Muehrcke's nails, half and half, nails, etc.

Muehrcke's nails were seen in total of 3 patients (2 fingernails and 1 toenail). Fingernail involvement was seen in patients on methotrexate and 6-mercaptopurine. The patient with involvement of toenails was on vincristine, daunomycin, 6-mercaptopurine, and methotrexate. Chromonychia was seen in one patient associated with beau's line and the patient was on methotrexate and 6-mercaptopurine [Table 4] and [Figure 3].
Figure 3: Graph showing various nail changes among study patients

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Table 4: Nail Changes in the Study Patients


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Steroid intake

A total of 37 patients were on steroids, out of which 28 (56%) were on dexamethasone, 18 (36%) on prednisolone, and 1 (2%) was on hydrocortisone.


  Discussion Top


This was a retrospective analysis of the spectrum of adverse effects associated with chemotherapy in children with hematological malignancies. Chemotherapeutic agents are commonly associated with mucocutaneous manifestations but the cause is difficult to determine. Because most of the patients were on more than one drugs and the disease conditions being life threatening, it was not possible to withdraw the treatment and ascertain the precise culprit agent. However, it was an effort to discover the spectrum of adverse effects of chemotherapy in pediatric hemato-oncology patients. Data regarding this subject is widely available for adults, but there is a paucity of literature when it comes to manifestations of chemotherapy in children.

Furthermore, mucocutaneous manifestations associated with chemotherapy are common but not well-known as physicians being concerned more with the anti-tumor efficacy of the treatment and other serious systemic adverse effects often tend to underestimate them. [4]

We analyzed 50 children for mucocutaneous manifestations. Majority of patients were suffering from B-cell ALL and T-cell ALL. Methotrexate, vincristine, 6-mercaptopurine, daunomycin, and asparaginase were the common drugs being administered. Twenty-three patients had cutaneous involvement whereas 24 patients had mucosae involvement. Seventeen patients had hair involvement whereas nails were involved in 26 patients.

Hyperpigmentation was the most common cutaneous side effect. The pattern of pigmentation ranged from diffuse to just involving the knuckles. Vincristine was a common agent among all the regimens, which led to hyperpigmentation. Acral hyperpigmentation (53.8%) and diffuse hyperpigmentation (38.4%) was a common pattern of cutaneous involvement in another similar study by Torres et al. [3]

In the present analysis, pyogenic abscess, tinea corporis, scabies, and pityriasis versicolor were noted infections among patients. Torres et al. [3] reported a high prevalence of fungal infections (25.6%), especially onychomycosis and ringworm, bacterial infections (25.6%), pediculosis (7.69%), and viral infections (5.12%), mainly herpes simplex and viral warts.

Aphthous ulcer followed by oral candidiasis and herpes labialis were the common mucosal changes. A high prevalence of mucositis (38.4%) has been reported by Torres et al., [3] and similar findings have been noted by other authors also. [5],[6]

Anagen effluvium (74.3%) was reported in higher number of patients by Torres et al
. than our study (34%). Chemotherapeutic agents used in cancer chemotherapy frequently cause alopecia, with anagen effluvium being the most common pattern. The mechanism involved is a sharp fall in mitotic activity of the matrix cells of the hair follicle due to cytotoxicity. [7] Alopecia is one of the manifestations with maximal psychological morbidity in patients. It is easily identifiable and cause distress, especially if made fun of by the fellow children.

Deformed and disfigured nails can cause embarrassment to children undergoing chemotherapy. We noted a variety of nail changes involving both fingernails and toenails including Beau's lines, melanonychia, leuconychia, Mees lines, Muehrcke's nails, half and half nails, etc., whereas a previous study only found Beau's lines. [3]


  Conclusion Top


The mucocutaneous manifestations associated with chemotherapy cause significant morbidity and possibly mortality in children. A proper knowledge of these manifestations can help in early identification and withdrawal of the offending agents and prevent the morbidity with appropriate and timely management.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneousreactions to chemotherapy. J AmAcad Dermatol 1999;40:367-98.  Back to cited text no. 1
    
2.
Wyatt AJ, Leonard GD, Sachs D. Cutaneous Reactions to chemotherapy and their Management. Am J Clin Dermatol 2006;7:45-63.  Back to cited text no. 2
    
3.
Cardoza-Torres MA, Liy-Wong C, Oliverio Welsh O, Gómez-Flores M, Ocampo-Candiani J, González-Llano O, et al. Skin manifestations associated with chemotherapy in children with hematologic malignancies. Pediatric Dermatol 2012;29:264-9.  Back to cited text no. 3
    
4.
Guillot B, Bessis D, Deureure O. Mucocutaneous side effects of antineoplastic chemotherapy. Expert Opinion Drug Saf 2004;3:579-87.  Back to cited text no. 4
    
5.
Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol 2002;14:212-6.  Back to cited text no. 5
    
6.
Carelle N, Piotto E, Bellanger A, Germanaud J, Thuillier A, Khayat D. Changing patient perceptions of the side effects of cancer chemotherapy. Cancer 2002;95:155-63.  Back to cited text no. 6
    
7.
Tosti A, Pazzaglia M. Drugs Reactions Affecting Hair: Diagnosis. Dermatol Clin 2007;25:223-31.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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