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E-IJD CASE REPORT
Year : 2016  |  Volume : 61  |  Issue : 1  |  Page : 122
Bleomycin containing chemotherapeutic regimen induced acquired partial lipodystrophy


1 Department of Pharmacology and Therapeutics, Government Medical College, Jammu, Jammu and Kashmir, India
2 Department of Radiotherapy, Government Medical College, Jammu, Jammu and Kashmir, India
3 Department of Dermatology, Government Medical College, Jammu, Jammu and Kashmir, India
4 Department of General Medicine, Government Medical College, Jammu, Jammu and Kashmir, India

Date of Web Publication15-Jan-2016

Correspondence Address:
Vishal R Tandon
Department of Pharmacology and Therapeutics, Government Medical College, Jammu, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.174133

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   Abstract 

Bleomycin toxicity predominantly affects the skin and lungs. Cutaneous toxicity classically known to present with bleomycin are flagellate erythema and drug rash. We hereby report an isolated case of (bleomyicn)-induced acquired partial (lipodytrophy) having potential cosmetic implications in a young women prescribed postoperatively following a case of germ cell carcinoma of ovary (endodermal sinus tumor).


Keywords: Bleomycin, cutaneous toxicity, lipodytrophy


How to cite this article:
Tandon VR, Gupte N, Mahajan V, Sharma R, Langer C, Khajuria V, Mahajan A. Bleomycin containing chemotherapeutic regimen induced acquired partial lipodystrophy. Indian J Dermatol 2016;61:122

How to cite this URL:
Tandon VR, Gupte N, Mahajan V, Sharma R, Langer C, Khajuria V, Mahajan A. Bleomycin containing chemotherapeutic regimen induced acquired partial lipodystrophy. Indian J Dermatol [serial online] 2016 [cited 2020 Sep 23];61:122. Available from: http://www.e-ijd.org/text.asp?2016/61/1/122/174133

What was known?
Cutaneous toxicities classically known to present with bleomycin are flagellate erythema, bullous dermatitis, pigmentation, Raynaud′s phenomenon, scleroderma, stomatitis, drug rash, hair, and the nails manifestations.



   Introduction Top


Bleomycin is an anti-neoplastic, anthracycline antibiotic used as a chemotherapeutic agent. Bleomycin toxicity predominantly affects the skin and lungs. [1] Bleomycin is used in (dermatology) for various skin cancers, warts, keloids, and scars, at the same time it is known to cause cutaneous side-effects resulting from its use. [2] Its cutaneous adverse effects are diverse. Cutaneous (toxicities) classically known to present with bleomycin are flagellate erythema bullous dermatitis, pigmentation, Raynaud's phenomenon, scleroderma, stomatitis, drug rash, hair, and the nails manifestations. [3]

The lipodystrophies are rare disorders characterized by selective but variable loss of adipose tissue. Lipodystrophy is a common manifestation in systemic lupus erythematosus nephritis, scleroderma, [4] Sjφgren syndrome, recurrent pyogenic infections, immune thrombocytopenic purpura, thyroiditis, and HIV. [5] Lipodystrophy is also a common complication in patients who are taking protease inhibitors, [6] insulin, corticosteroids, IM penicillin G, iron dextran, diphtheria/pertussis/tetanus (DPT) vaccine, and recombinant growth hormone. [5]

Although, cutaneous toxicity is known to exist with the use of bleomycin, to the best of our knowledge there exists no isolated case report presenting as bleomyicn-induced lipodystrophy having potential cosmetic implications in women.


   Case Report Top


We hereby report bleomyicn-induced lipodystrophy in 20-year-old female; weight 48 kg, height 1.65 m diagnosed with a case of germ cell carcinoma of the ovary (endodermal sinus tumor) reported in Adverse Drug Reaction Monitoring (Under PvPI) Centre vde no. 423/250211/ADRM.

Preoperative cancer marker levels were as follows: CA-125 = 26.6 U/ml; alpha fetoprotein = 3765 ng/ml; human chorionic gonadotropin <1 mIU/mL. Ultrasonography (USG) helped in establishing the diagnosis of an ovarian tumor/mass. Postoperative histopathological findings confirmed it as a case of germ cell carcinoma of the ovary (endodermal sinus tumor, also known as a yolk sac tumor).

Postoperatively, the patient was started with injections of bleomycin (30 mg/m 2 D1, D8 and D15); injections of etposide (100 mg/m 2 I.V. D1 and D5) and cisplatin (20 mg/m 2 I.V. D1 and D5) combination in cyclic manner. The patient developed acquired partial lipodystrophy with subcutaneous fat loss limited to the trunk and left side of the back within 3 days of the first cycle [Figure 1], [Figure 2] and [Figure 3]. The patient had no history of smoking, alcohol consumption, any substance abuse, associated pathology, concurrent drug or vaccine intake.
Figure 1: Bleomycin-induced acquired partial lipodystrophy on abdomen

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Figure 2: Bleomycin-induced acquired partial lipodystrophy on back

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Figure 3: Bleomycin-induced acquired partial lipodystrophy on left lateral side of back

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There was no history of such an episode in the past. Clinical examination revealed no rheumatological, nephrological, neurological or liver problem present. Investigations revealed a normal chest skiagram. All basic investigations including complete blood count, hemoglobin, erythrocyte sedimentation rate, routine urine, stool examination, blood sugar, liver function test, renal function test, lipid profile, electrocardiogram, and USG were found to be normal. The HIV status of the patient was negative.

Since the adverse drug reaction (ADR) was not serious and had only cosmetic implications in the young woman, the patient was continued with the same drugs in cyclic manner and the cause of the ADR was most likely thought to be associated with bleomycin because of its known cutaneous toxicities. [1],[2],[3]

Dechallenge of the bleomycin during chemotherapy recovery phase caused the ADR to ameliorate. Further rechallenge resulted in the reappearance of the ADR during next cycle. No treatment was given to the patient, and she is still on follow-up. Thus, the appearance of bleomycin-induced partial lipodystrophy could not be explained by a concurrent disease, other drug or chemicals. Dechallenge improved the condition and rechallenge resulted in reappearance of the ADR. On literature search there is no similar report of such ADR. However, skin toxicities are well-known with bleomycin. [1],[2],[3]


   Discussion Top


This ADR can be labeled "Probable" with a score of 7 on Naranjo's scale for causality assessment as per causality assessment. [7] Since this ADR was not studied for dose dependent response and was unpredictable/unusual it could be clearly labeled as a Type-B class of ADR. [8]

Lipodystrophy is of two types: Familial and acquired. [5] Patients can present as acquired generalized lipodystrophy or partial lipodystrophy. Both varieties occur approximately 3 times more often in women. Lipodystrophy is also a common complication in patients on protease inhibitors, [6] insulin, corticosteroids, IM penicillin G, iron dextran, DPT vaccine, and recombinant growth hormone. [5]

Management of these patients includes cosmetic surgery, diet, and drug therapy for control of associated dyslipidemia if any. No treatment was offered in the current patient. The mechanism of this adverse reaction is not clear. However, the possibility of an autoimmune reaction resulting into a cutaneous manifestation in the form of lipodystrophy appears to be the likely possibility in view of its time relationship.


   Conclusion Top


The current ADR highlights the need to create awareness by oncologist/physicians for patients receiving bleomycin to ameliorate the dual psychological trauma as result of ongoing pathology and due to cosmetically unacceptable ADR in the form of lipodystrophy before initiation of the treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Fyfe AJ, McKay P. Toxicities associated with bleomycin. J R Coll Physicians Edinb 2010;40:213-5.  Back to cited text no. 1
    
2.
Yamamoto T. Bleomycin and the skin. Br J Dermatol 2006;155:869-75.  Back to cited text no. 2
    
3.
Pasquet F, Pavic M, Estival JL, Karkowski L, Debourdeau P. Flagellate erythema: An uncommon side effect of bleomycin. Rev Med Interne 2009;30:637-9.  Back to cited text no. 3
    
4.
Yachoui R, Traisak P, Jagga S. Scleredema in a patient with AIDS-related lipodystrophy syndrome. Case Rep Endocrinol 2013;2013:943798.  Back to cited text no. 4
    
5.
Garg A. Lipodystrophies. Am J Med 2000;108:143-52.  Back to cited text no. 5
    
6.
Piloya T, Bakeera-Kitaka S, Kekitiinwa A, Kamya MR. Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: A cross sectional study. J Int AIDS Soc 2012;15:17427.  Back to cited text no. 6
    
7.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 7
[PUBMED]    
8.
Edwards IR, Aronson JK. Adverse drug reactions: Definitions, diagnosis, and management. Lancet 2000;356:1255-9.  Back to cited text no. 8
    

What is new?
To best of our knowledge, this is the first report of bleomycin-induced acquired partial lipodystrophy having potential cosmetic implications in a young woman.


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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    Abstract
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