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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2019  |  Volume : 30  |  Issue : 4  |  Page : 978-981
Cyclophosphamide-induced melanonychia in a patient with steroid dependent nephrotic syndrome: A rare presentation


Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

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Date of Submission24-Aug-2018
Date of Acceptance24-Sep-2018
Date of Web Publication27-Aug-2019
 

   Abstract 


Melanonychia is described as a brown to black pigmentation of nail, due to stimulation and hyperplasia of nail matrix. Various systemic disorders, trauma, inflammatory disorders, fungal infections, drugs, benign melanocytic hyperplasia, etc., are responsible for this condition, and most of them are benign. A number of chemotherapeutic agents can cause melanonychia. Cases of cyclophosphamide-induced melanonychia are not frequent. We report a 38-year-old female, a known case of steroid dependent nephrotic syndrome, who developed melanonychia on starting treatment with cyclophosphamide. It is a benign condition, which resolves on discontinuation of the drug.

How to cite this article:
Mehta S, Makkar V, Soha P M, Sethi S, Kaur S. Cyclophosphamide-induced melanonychia in a patient with steroid dependent nephrotic syndrome: A rare presentation. Saudi J Kidney Dis Transpl 2019;30:978-81

How to cite this URL:
Mehta S, Makkar V, Soha P M, Sethi S, Kaur S. Cyclophosphamide-induced melanonychia in a patient with steroid dependent nephrotic syndrome: A rare presentation. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Nov 17];30:978-81. Available from: http://www.sjkdt.org/text.asp?2019/30/4/978/265478



   Introduction Top


Melanonychia is described as a brown to black pigmentation of nail. It may be due to stimulation and hyperplasia of nail matrix, invasion of nail by melanin-producing pathogens, subungual hemorrhage, and also, due to drugs.[1],[2],[3],[4],[5] Drug-induced melanonychia usually affects numerous nails and appears as multiple light brown to black longitudinal or transverse bands or diffuse nail discoloration.[6] This depends on the type of melanocytic activation; in case of cluster activation, it will present as single longitudinal pigmented bands while diffuse activation will result in discoloration of the whole nail.[6],[7] A number of chemotherapeu- tic agents are associated with melanonychia- like abnormality: bleomycin sulfate, cyclo- phosphamide, and methotrexate. There is no specific treatment for melanonychia, it is a self-limiting problem and regresses slowly on discontinuation of the offending agent. The discoloration subsides as the nail grows; however, it takes a long time depending on the severity of toxicity, the dose and duration of drug use, and also the time of cessation of the offending agent. Patients who are worried about the appearance of the nails can mask it using cosmetics like nail polish. The cases of cyclophosphamide-induced melanonychia are not frequent. Only few cases have been reported in the literature.


   Case Report Top


Written informed consent was obtained from the patient before reporting the case.

A 38-year-old female, a known case of steroid-dependent nephrotic syndrome, on treatment with cyclophosphamide, presented with gradually progressive pigmentation of the nails of all four limbs, starting from the upper limb and gradually involving the lower limbs, of six weeks’ duration [Figure 1], [Figure 2], [Figure 3]. This was associated with hyperpigmentation of the knuckles. This pigmentation was asymptomatic and not preceded by any inflammatory lesion. There was no pigmentation of the oral mucosa and/or any other abnormal pigmented lesion anywhere in the body. There was no family history of similar lesions, any oral mucosal or lip pigmentation, or polyposis. All the finger nails and toe nails were diffusely pigmented without discrete band appearance. Blackish discoloration spread onto the proximal nail folds from all the nails. No pitting or any history of any inflammation or injury to the nail was recognized. There was no history of any abnormal pigmentation of palms, soles, and genitals. She was diagnosed to have nephrotic syndrome 15 months back, when she presented with swelling of both lower limbs and frothiness of urine. Her urine routine revealed 3+ proteinuria, spot urine protein–creatinine ratio was 9.8, serum cholesterol 487 mg/dL, triglycerides 322 mg/dL, LDL 314 mg/dL, hemoglobin 13 g/dL, total white cell count 5700 (neutrophils – 52%, lymphocytes – 40%, monocytes – 4%, eosinophils – 2%, basophils – 2%), platelets 2.48 lakh, urea 22 mg/dL, creatinine 0.7 mg/dL, serum protein 6.9 mg/ dL, albumin 2.2 g/dL, sodium 137 mmol/L, potassium 5.5 mmol/L, total bilirubin 0.29 mg/dL, direct 3.9 mg/dL, glutamate transaminase 15 U/L, pyruvate transaminase 9 U/L, alkaline phosphatase 101 U/L, calcium 8.5 mg/dL, phosphorus 3.9 mg/dL, and uric acid 5.1 mg/dL. Her antinuclear antibody was negative by immunofluorescence, viral markers were nonreactive by ELISA, and the thyroid profile and complement levels were normal.
Figure 1: Clinical photograph showing melanonychia of all fingers of both upper limbs along with hyperpigmentation of knuckles.

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Figure 2: Clinical photograph of hands showing melanonychia of both thumbs.

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Figure 3: Clinical photograph of both feet showing melanonychia of the digits of lower limbs.

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Renal biopsy was suggestive of adult onset minimal change disease. She was diagnosed as adult-onset nephrotic syndrome with minimal change disease and started on oral steroids 60 mg/day. She achieved remission, and steroids were tapered gradually. While tapering the steroid dosage, she developed relapse of the nephrotic syndrome, and steroid dosage was increased. She was treated as steroid- dependent nephrotic syndrome and was started on cyclophosphamide 150 mg/day as steroid- sparing agent. She achieved remission. Six weeks after starting cyclophosphamide, she developed gradually progressive blackish pigmentation of the nail of all four limbs along with hyperpigmentation of knuckles. Her general physical and systemic examination was normal. The investigations did not reveal any abnormality. This blackish pigmentation, melanonychia, was attributed to cyclophos- phamide, given the temporal association of six weeks after starting the drug. In view of the benign nature of the lesion and the need to maintain remission, cyclophosphamide was continued.


   Discussion Top


Melanonychia is brown or black pigmentation of the nail unit. Various causes have been described including physiologic longitudinal melanonychia, systemic disorders, trauma, inflammatory disorders, fungal infections, drugs, and benign melanocytic hyperplasia and chronic inflammatory conditions such as onychomycosis, paronychia, psoriasis, lichen planus, amyloidosis, and chronic radio derma- titis.[4] Certain diseases such as Addison’s disease, Albright syndrome, Lichen planus, drugs, cyanocobalamine deficiency, and AIDS are commonly accompanied by cutaneous and mucosal pigmentation.[4],[8] Medications (especially chemotherapeutic agents),[9],[10] phototherapy, X-ray exposure, and electron beam therapy[4],[11] are important causes of iatrogeni- cally induced melanonychia. Syndrome-associated melanonychia, which occurs in conjunction with Laugier-Hunziker, Peutz-Jeghers, and Touraine syndromes, typically involves multiple digits and also mucosal pigmented macules involving the lips and oral cavity.[4] A number of chemotherapeutic agents are associated with melanonychia such as dacarbazine doxorubicin, etoposide, five-fluorouracile, hydroxyurea, imatinib, melphalan hydrochlo- ride, daunorubicin hydrochloride, nitrogen mustard, nitrosourea, busulfan, and tegafur.[3],[6]

In some cases, melanonychia may be a presenting feature of nail apparatus melanoma (NAM), and thus, biopsy of melanonychia should be performed to confirm whether it is due to melanoma or a result of other factors. NAM[3],[4],[12] usually involves a single digit; mainly the thumb, index finger, or the great toe. It develops after the age of 40 years or more and is associated with a history of digital trauma and family or previous history of melanoma or dysplastic nevus. NAM is suspected if there is no possible explanation for the melanonychia of the nail and presence of the features mentioned above, and a biopsy is performed for confirmation. In our patient, there was no need for biopsy since she had discoloration of all the nails of the hands and toes rather than single digit involvement, and also, the patient did not have any family or personal history of melanoma or dysplastic nevus, and also, the nail discoloration was not associated with any history of digital trauma, thus ruling out the possibility of NAM.

There are few reports on cyclophosphamide- induced nail pigmentation wherein it has been reported that cyclophosphamide may cause purple, brown, or black discoloration with different pattern ranging from diffuse to transverse to longitudinal.[1],[2],[6],[13] Cyclophosphamide, an alkylating agent, acts by introducing an alkyl group to the DNA strand resulting in the DNA cross-linkage leading to disruption of DNA replication and stopping cancer cells from growing. It also has immunosuppressant activity; it has cytotoxic effect on lymphocytes. There are many mechanisms proposed for cyclophosphamide-induced nail pigmentation such as genetic predisposition, toxicity to the nail bed and matrix, focal activation of melanocytic matrix, and photosensitization. There is no specific treatment for melano- nychia; it is self-limiting and regresses slowly on discontinuation of the offending agent. The discoloration subsides as the nail grows although it takes a long duration depending on the severity of toxicity, the dose and duration of drug use, and also, the time of cessation of the offending agent. Patients who are worried about the appearance of the nails can mask it using cosmetics like nail polish.

In conclusion, cyclophosphamide-induced nail discoloration is a rare adverse event that is underreported. It is not associated with any deleterious effect to patient health and only affects the physical appearance of the nails. It resolves on the completion of therapy or discontinuation of the offending agent as the new nails grow.

Conflict of interest: None declared.



 
   References Top

1.
Lopes M, Jordão C, Grynszpan R, Sodré C, Ramos-E-Silva M. Chromonychia secondary to chemotherapy. Case Rep Dermatol 2013;5: 163-7.  Back to cited text no. 1
    
2.
Kumar S, Dixit R, Karmakar S, Paul S. Unusual nail pigmentation following cyclophosphamide-containing chemotherapy regimen. Indian J Pharmacol 2010;42:243-4.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Jefferson J, Rich P. Melanonychia. Dermatol Res Pract 2012;2012:952186.  Back to cited text no. 3
    
4.
Haneke E, Baran R. Longitudinal melanonychia. Dermatol Surg 2001;27:580-4.  Back to cited text no. 4
    
5.
André J, Lateur N. Pigmented nail disorders. Dermatol Clin 2006;24:329-39.  Back to cited text no. 5
    
6.
Gilbar P, Hain A, Peereboom VM. Nail toxicity induced by cancer chemotherapy. J Oncol Pharm Pract 2009;15:143-55.  Back to cited text no. 6
    
7.
Piraccini BM, Tosti A. Drug-induced nail disorders: Incidence, management and prognosis. Drug Saf 1999;21:187-201.  Back to cited text no. 7
    
8.
Cribier B, Mena ML, Rey D, et al. Nail changes in patients infected with human immunodeficiency virus. A prospective controlled study. Arch Dermatol 1998;134:1216- 20.  Back to cited text no. 8
    
9.
Kar HK. Longitudinal melanonychia associated with fluconazole therapy. Int J Dermatol 1998;37:719-20.  Back to cited text no. 9
    
10.
O’branski EE, Ware RE, Prose NS, Kinney TR. Skin and nail changes in children with sickle cell anemia receiving hydroxyurea therapy. J Am Acad Dermatol 2001;44:859-61.  Back to cited text no. 10
    
11.
Quinlan KE, Janiga JJ, Baran R, Lim HW. Transverse melanonychia secondary to total skin electron beam therapy: A report of 3 cases. J Am Acad Dermatol 2005;53:S112-4.  Back to cited text no. 11
    
12.
Rich P. Nail surgery in dermatology. In: Bolognia JL, Jorizo JL, Rapini RP, editors. 2nd ed. New York: Mosby; 2006. p. 2260-8.  Back to cited text no. 12
    
13.
Ranawaka RR. Patterns of chromonychia during chemotherapy in patients with skin type V and outcome after 1 year of follow-up. Clin Exp Dermatol 2009;34:e920-6.  Back to cited text no. 13
    

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Correspondence Address:
Vikas Makkar
Department of Nephrology, Dayanand Medical College and Hospital, Ludhiana, Punjab
India
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DOI: 10.4103/1319-2442.265478

PMID: 31464259

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    Abstract
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