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Table of Contents 
CASE REPORT
Year : 2019  |  Volume : 64  |  Issue : 4  |  Page : 321-323
Pompholyx-like eruptions induced by penicillamine in a patient with wilson's disease


1 Department of Dermatology, St. Johns Medical College Hospital, Bengaluru, Karnataka, India
2 Department of Gastroenterology, St. Johns Medical College Hospital, Bengaluru, Karnataka, India

Date of Web Publication5-Jul-2019

Correspondence Address:
Diana Elizabeth Devassy
Department of Dermatology, St. Johns Medical College Hospital, Sarjapur Road, Bengaluru - 560 034, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_328_18

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   Abstract 


Wilson's disease is an inherited disorder of copper metabolism that results in excessive accumulation of copper in various organs, with liver being the primary site of involvement. D-penicillamine (DPA) as a chelating agent forms the mainstay of therapy; however, it can cause a myriad of adverse effects on long-term use. The major adverse effects reported with DPA include disorders of collagen synthesis, such as pseudoxanthoma elasticum-like lesions, autoimmune blistering diseases, and urticarial lesions. Here, we report a young girl who developed extensive pompholyx-like blisters within a few months of starting DPA which on histopathology showed a spongiotic reaction. The lesions improved on stopping DPA and initiation of oral steroids.


Keywords: D-penicillamine, drug rash, pompholyx, Wilson's disease


How to cite this article:
Devassy DE, Harshad SR, Devarbhai H. Pompholyx-like eruptions induced by penicillamine in a patient with wilson's disease. Indian J Dermatol 2019;64:321-3

How to cite this URL:
Devassy DE, Harshad SR, Devarbhai H. Pompholyx-like eruptions induced by penicillamine in a patient with wilson's disease. Indian J Dermatol [serial online] 2019 [cited 2019 Jul 17];64:321-3. Available from: http://www.e-ijd.org/text.asp?2019/64/4/321/262168





   Introduction Top


Wilson's disease is a rare autosomal recessive disease caused by a defect in ATP7B gene leading to defective ceruloplasmin formation and thereby causing derangement in cellular copper transport.[1] Subsequent accumulation of copper causes damage and dysfunction of various organs, with liver being the primary site of involvement. Penicillamine, a metabolic by-product of penicillin that avidly chelates copper, was introduced as a treatment for Wilson's disease by Walshe in 1956 and quickly became the standard therapy.[2] Cutaneous reactions which are the most common adverse effect are seen in 25%–50% of all patients treated with penicillamine,[3],[4] but treatment cessation has been needed only in 10% of patients.[4],[5],[6] The skin reactions may be due to interference with collagen synthesis, acute sensitivity reactions such as urticaria, autoimmune blistering diseases, and dermatoses due to uncertain mechanisms such as psoriasiform dermatitis.[7] Here, we report a case of spongiotic dermatitis in a patient of Wilson's disease due to penicillamine.


   Case Report Top


A 19-year-old girl who was diagnosed with Wilson's disease 5 months ago presented to us with acute eruption of pruritic, tense, clear fluid-filled vesicles, and bullae over the forearms and lower abdomen [Figure 1]. The lesions rapidly progressed in number, size, and extent to involve the entire trunk, upper thighs, face, palms, and soles [Figure 2]. Oral and genital mucosae were spared, and Nikolsky's sign could not be elicited.
Figure 1: Tense clear fluid-filled bullae and vesicles on the abdomen

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Figure 2: Pompholyx-like eruption noted over the palms

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Tzanck smear done showed only eosinophils and neutrophils, but acantholytic cells were absent. Skin biopsy from bulla revealed spongiosis with an intraepidermal vesicle containing fibrin, eosinophils, and neutrophils. The dermis showed mild perivascular inflammatory response with eosinophils [Figure 3]. Direct immunofluorescence showed negativity for all reactants. We did culture and sensitivity tests from blister fluid which showed no growth. As this reaction belonged to the nonimmediate type of hypersensitivity reaction, IgE levels were not measured.
Figure 3: Clearing of lesions within a week of stopping penicillamine and starting corticosteroids

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The patient was recently detected to have Wilson's disease with liver failure and had been started treatment with D-penicillamine (DPA) 250 mg two times a day and spironolactone with furosemide for the past 4 months. Lesions developed after 1 month of starting the above drugs. Initially, we stopped furosemide and continued DPA; however, due to the continued progression of the lesions, we discontinued DPA after 2 days. The patient was treated with oral prednisolone 40 mg which was tapered and stopped over the next 2 weeks. There was a rapid improvement in her skin lesions with complete resolution in 2 weeks [Figure 4]. Oral zinc sulfate was started as alternative chelating agent, and furosemide with spironolactone was reintroduced at a later date. Till date, there has been no recurrence of bullous eruption, and the patient is doing well on zinc therapy. Lymphocyte transformation test was not done due to nonavailability, and a patch test could have been performed; however, as the patient was being managed on zinc currently, we did not attempt it.
Figure 4: Intraepidermal vesicles containing fibrin, eosinophils, and neutrophils with spongiosis (H & E, ×100)

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   Discussion Top


Cutaneous side effects of DPA may be divided into several categories based on their mechanism of induction as follows:[7]

  1. Dermatoses that result from interference with collagen and elastin crosslinking-


  2. DPA condenses with the aldehyde and ketone groups in tropocollagen forming thiazolidine rings. This inhibits aldol crosslinking of collagen and elastin fibers. In long-term, high-dose treatment, it can lead to skin fragility, friction bullae, acquired cutis laxa, elastosis perforans serpiginosa, and pseudoxanthoma elasticum

  3. Acute sensitivity reactions such as urticaria and maculopapular rash - These have been reported to occur in 15% of patients treated with DPA and arise usually after 7 to 10 days of starting therapy with prompt resolution on discontinuation of the drug [8],[9],[10]
  4. Autoimmune-mediated dermatoses -


  5. The acantholytic property of DPA results in exposure of antigens that are foreign to the immune system and generates an autoimmune reaction. This may explain its ability to trigger pemphigus group of disorders. DPA may also act as a hapten, and by binding to cell surface molecules through thiol-disulfide interchange, it causes structural modification of the epidermis and trigger an autoimmune response.

  6. Dermatoses that result from an uncertain mechanism such as lichen planus, psoriasiform dermatoses, seborrheic dermatitis, lichen planus, and alopecia areata.


Fewer than 15 cases of bullous pemphigoid have been reported with DPA,[11],[12],[13],[14],[15],[16] numerous cases belonging to pemphigus spectrum have been reported, the first case being reported in 1969. Occasionally, combined features of pemphigus and pemphigoid induced by DPA have also been reported. For example, Velthuis et al. reported a case with clinical, histologic, and immunologic features of pemphigus [13] and in vivo IgG bound to the dermoepidermal junction, and Troy et al.[12] reported a case with the histologic features of pemphigus and the immunofluorescence findings of bullous pemphigoid. Cicatricial pemphigoid and epidermolysis bullosa acquisita-like lesions have also been reported in patients taking DPA.

In our patient, the standout features were the onset of severely pruritic lesions within a few months of initiating DPA with the involvement of palms and soles, lack of acantholytic cells on Tzanck smear and biopsy, intraepidermal vesiculation with spongiosis and direct immunofluorescence being negative (thus ruling out an autoimmune cause for the eruption).

The lesions dramatically responded on discontinuing DPA and initiation of short course of oral steroids. There has been no recurrence of lesions on follow-up, and we have not done a rechallenge with DPA as the patient is doing well on oral zinc therapy.


   Conclusion Top


This case is being reported as there has been no previous report on a spongiotic eruption with pompholyx-like features secondary to penicillamine in a patient with Wilson's disease. Based on the Naranjo's score for the adverse reaction, a score of 6 was given to this case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Das SK, Ray K. Wilson's disease: An update. Nat Clin Pract Neurol 2006;2:482-93.  Back to cited text no. 1
    
2.
Walshe JM. Penicillamine, a new oral therapy for Wilson's disease. Am J Med 1956;21:487-95.  Back to cited text no. 2
    
3.
Howard-Lock HE, Lock CJ, Mewa A, Kean WF. D-penicillamine: Chemistry and clinical use in rheumatic disease. Semin Arthritis Rheum 1986;15:261-81.  Back to cited text no. 3
    
4.
Stein HB, Patterson AC, Offer RC, Atkins CJ, Teufel A, Robinson HS, et al. Adverse effects of D-penicillamine in rheumatoid arthritis. Ann Intern Med 1980;92:24-9.  Back to cited text no. 4
    
5.
Situnayake RD, Grindulis KA, McConkey B. Long-term treatment of rheumatoid arthritis with sulphasalazine, gold, or penicillamine: A comparison using life-table methods. Ann Rheum Dis 1987;46:177-83.  Back to cited text no. 5
    
6.
Capell HA, Marabani M, Madhok R, Torley H, Hunter JA. Degree and extent of response to sulphasalazine or penicillamine therapy for rheumatoid arthritis: Results from a routine clinical environment over a two-year period. Q J Med 1990;75:335-44.  Back to cited text no. 6
    
7.
Levy RS, Fisher M, Alter JN. Penicillamine: Review and cutaneous manifestations. J Am Acad Dermatol 1983;8:548-58.  Back to cited text no. 7
    
8.
Walshe JM. Toxic reactions to penicillamine in patients with Wilson's disease. Postgrad Med J 1968;44:6-8.  Back to cited text no. 8
    
9.
Sternlieb I, Scheinberg IH. Penicillamine therapy for hepatolenticular degeneration. JAMA 1964;189:748-54.  Back to cited text no. 9
    
10.
Scheinberg IH. Toxicity of penicillamine. Postgrad Med J 1964;44:11-3.  Back to cited text no. 10
    
11.
Pegum JS, Pembroke AC. Benign mucous-membrane pemphigoid associated with penicillamine treatment. Br Med J 1977;1:1473.  Back to cited text no. 11
    
12.
Troy JL, Silvers DN, Grossman ME, Jaffe IA. Penicillamine-associated pemphigus: Is it really pemphigus? J Am Acad Dermatol 1981;4:547-55.  Back to cited text no. 12
    
13.
Velthuis PJ, Hendrikse JC, Nefkens JJ. Combined features of pemphigus and pemphigoid induced by penicillamine. Br J Dermatol 1985;112:615-9.  Back to cited text no. 13
    
14.
Rasmussen HB, Jepsen LV, Brandrup F. Penicillamine-induced bullous pemphigoid with pemphigus-like antibodies. J Cutan Pathol 1989;16:154-7.  Back to cited text no. 14
    
15.
Weller R, White MI. Penicillamine in the etiology of bullous pemphigoid. Ann Pharmacother 1998;32:1368.  Back to cited text no. 15
    
16.
Weller R, White MI. Bullous pemphigoid and penicillamine. Clin Exp Dermatol 1996;21:121-2.  Back to cited text no. 16
    


    Figures

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



 

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