|Year : 2019 | Volume
| Issue : 2 | Page : 107-109
D-penicillamine-induced elastosis perforans serpiginosa in a case of Wilson's disease
Shefali Saini1, Vidya D Kharkar1, Aabha Nagral2
1 Department of Dermatology, Venereology and Leprosy, Seth G.S. Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 Department of Gastroenterology, Jaslok Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||16-Dec-2019|
Dr. Shefali Saini
Room No. 905, UG/PG Hostel, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
The use of D-penicillamine has been well established in various disorders, mainly Wilson's disease, cystinuria, and rheumatoid arthritis. Elastosis perforans serpiginosa (EPS) is a rare perforating dermatosis, occurring as an uncommon sequel of long-term high-dose D-penicillamine therapy. We present a rare case of EPS in a known case of Wilson's Disease on D-penicillamine therapy. Biopsy revealed characteristic “lumpy-bumpy” elastic fibers, a finding specific to penicillamine-induced EPS.
Keywords: D-Penicillamine, elastosis perforans serpiginosa, Wilson's disease
|How to cite this article:|
Saini S, Kharkar VD, Nagral A. D-penicillamine-induced elastosis perforans serpiginosa in a case of Wilson's disease. Indian J Drugs Dermatol 2019;5:107-9
|How to cite this URL:|
Saini S, Kharkar VD, Nagral A. D-penicillamine-induced elastosis perforans serpiginosa in a case of Wilson's disease. Indian J Drugs Dermatol [serial online] 2019 [cited 2020 Jun 1];5:107-9. Available from: http://www.ijdd.in/text.asp?2019/5/2/107/272964
| Introduction|| |
Elastosis perforans serpiginosa (EPS) is classified as one of the four primary perforating dermatoses along with reactive perforating collagenosis, perforating folliculitis, and Kyrle disease. It occurs in three main forms – (1) idiopathic; (2) reactive with associated connective tissue diseases such as pseudoxanthoma elasticum (PXE), Ehlers–Danlos syndrome, cutis laxa, Marfan syndrome, osteogenesis imperfecta, and Down's syndrome; and (3) D-penicillamine induced. It is characterized by transepidermal elimination of fragmented elastic fibers, clinically presenting as hyperkeratotic papules configured in arciform or serpiginous patterns. We present one such interesting case of EPS in a patient of Wilson's Disease on D-penicillamine therapy with histopathology showing classic “lumpy-bumpy” elastic fibers, a feature seen only in the D-penicillamine-induced form and not in the idiopathic or reactive forms.
| Case Report|| |
A 32-year-old female presented with raised, mildly itchy lesions over both the forearms for 1 year [Figure 1]. The lesions started over the right forearm and then appeared over the left forearm in a span of 2–3 months with a gradual increase in size and central clearing. She was a known case of Wilson's disease since the age of 19 years and was being treated with D-penicillamine (0.5–1.5 g) since then. Examination revealed multiple hyperpigmented papules with central keratotic plugging, forming annular-to-serpiginous plaques varying in size from 1 to 5 cm with central atrophy and hyperpigmentation [Figure 1]. Skin biopsy from a papule showed a localized intraepidermal collection of inflammatory cells with hyperplastic damaged connective tissue fibers [Figure 2] and [Figure 3]. These were confirmed to be elastic fibers on staining with Verhoeff-van Gieson stain. At higher magnification, the striking feature of multiple serrations and buds arising perpendicularly from the borders of the elastic fibers was seen which clinched the diagnosis of penicillamine-induced EPS [Figure 4].
|Figure 1: Serpiginous plaques distributed symmetrically over the forearms comprising hyperpigmented papules with small central keratotic plugging, the center of the plaques showing mild atrophy and hyperpigmentation|
Click here to view
|Figure 2: Acanthotic epidermis with a localized intraepidermal collection of inflammatory cells and coarse basophilic connective tissue debris (H and E, ×10)|
Click here to view
|Figure 3: A localized intraepidermal collection of abundant thickened, coarse, basophilic connective tissue fibers with mixed inflammatory infiltrate. Similar changes observed in the papillary dermis (H and E, ×20)|
Click here to view
|Figure 4: “Lumpy-bumpy” elastic tissue fibers with multiple serrations arising perpendicularly from the borders of the fibers (arrows) (Verhoeff-van Gieson, ×40)|
Click here to view
It was noted that the biopsy site showed a complete resolution with no keloid formation or recurrence. This prompted us to do serial punch excisions of prominent lesions along with topical 0.05% tretinoin cream application over a period of 8 months. During this time, penicillamine was stopped by the treating physician in view of the improvement in the signs and symptoms of Wilson's disease in the patient. At the 18-month follow–up, most of the keratotic papules had subsided with residual hyperpigmentation and mild atrophy [Figure 5].
|Figure 5: Posttreatment photo at 18-month follow-up showing subsidence of majority of the papules with residual hyperpigmentation and mild atrophy|
Click here to view
| Discussion|| |
Long-term administration of D-penicillamine has been shown to produce a dermatopathy in 20%–33% of patients in addition to hematological, immunological, and other organ system involvement. Cutaneous side effects can be classified into four distinct groups: acute sensitivity reactions (e.g. acute urticaria), a toxic-metabolic effect on connective tissue or degenerative dermopathy (penicillamine-induced skin fragility, cutis laxa, EPS, anetoderma, and PXE), autoimmune skin manifestations (e.g. pemphigus, lupus erythematosus, and dermatomyositis), and those due to unknown mechanisms (e.g. lichen planus and hypertrichosis). The mechanism of D-penicillamine-induced elastic tissue damage in EPS is unknown; however, there are several theories. Since D-penicillamine chelates copper and is concentrated in the skin, a local copper deficiency could theoretically inhibit the copper-dependent enzyme lysyl oxidase, required for the production of elastin fiber cross-linking. However, in Menkes' kinky hair syndrome, a disease of copper deficiency resulting from defective copper absorption, neither EPS nor elastic tissue changes in skin are known to occur. Other theories such as direct blockage of the aldehyde cross-link precursors have also been proposed. D-penicillamine, however, has no effect on mature, insoluble collagen, therefore explaining the long period before dermopathy sets in. It has been estimated that a minimum of 1 g daily for more than 5 years is necessary to induce these changes. However, a study by Dalziel et al. showed that elastic fiber damage occurred in rheumatoid arthritis patients receiving low-dose penicillamine therapy (0.25–1 g daily), even after as little as 1 year of treatment.
The characteristic histopathology of penicillamine-induced elastic fiber damage is that of thickened elastic fiber bundles with prominent lateral protrusions giving the so-called “lumpy-bumpy” or “bramble-bush” appearance., Transepidermal elimination of elastic fibers may occur that manifests clinically as EPS. This feature present in our case helped clinch the diagnosis unmistakably. Similar elastic fiber changes have been reported in the nonlesional skin, lung, aorta, and other organ systems.
Numerous treatment modalities have been described, although none is considered as the gold standard. Moderately effective treatments include cryotherapy, oral isotretinoin, cellophane tape stripping, and topical tazarotene gel and imiquimod cream. Recently, there have been reports of the successful use of fractional carbon dioxide laser.
Excision and dermabrasion are usually avoided due to the high chances of keloid formation. However, in our patient, complete clearance with no recurrence or keloid at the biopsy site prompted us to perform serial punch excisions along with topical tretinoin cream application, and the results were found to be satisfactory.
The novelty of our case report lies in highlighting the fact that a timely stoppage of the drug may halt the disease process and prevent a recurrence. Moreover, there are limited reports of using punch excisions for treatment which, in our case, coupled with cessation of the drug, helped achieve significant improvement. Hence, this modality may be considered as a viable treatment option at least in those patients in whom penicillamine therapy has been stopped.
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
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bardach H, Gebhart W, Niebauer G. “Lumpy-bumpy” elastic fibers in the skin and lungs of a patient with a penicillamine-induced elastosis perforans serpiginosa. J Cutan Pathol 1979;6:243-52.
Iozumi K, Nakagawa H, Tamaki K. Penicillamine-induced degenerative dermatoses: Report of a case and brief review of such dermatoses. J Dermatol 1997;24:458-65.
Khandpur S, Jain N, Singla S, Chatterjee P, Behari M. D-penicillamine induced degenerative dermopathy. Indian J Dermatol 2015;60:406-9.
] [Full text]
Reymond JL, Stoebner P, Zambelli P, Beani JC, Amblard P. Penicillamine induced elastosis perforans serpiginosa: An ultrastructural study of two cases. J Cutan Pathol 1982;9:352-7.
Hashimoto K, McEvoy B, Belcher R. Ultrastructure of penicillamine-induced skin lesions. J Am Acad Dermatol 1981;4:300-15.
Meyrick Thomas RH, Kirby JD. Elastosis perforans serpiginosa and pseudoxanthoma elasticum-like skin change due to D-penicillamine. Clin Exp Dermatol 1985;10:386-91.
Dalziel KL, Burge SM, Frith PA, Ryan TJ, Mowat A. Elastic fibre damage induced by low-dose D-penicillamine. Br J Dermatol 1990;123:305-12.
Lund HZ, Leonard DD, Briggaman RA, Pool R. The peculiar fibers found in perforating elastosis associated with penicillamine-treated Wilson's disease. Arch Dermatol 1979;115:1347.
Khatu SS, Dhurat RS, Nayak CS, Pereira RR, Kagne RB. Penicillamine-induced elastosis perforans serpiginosa with abnormal “lumpy-bumpy” elastic fibers in lesional and non-lesional skin. Indian J Dermatol Venereol Leprol 2011;77:55-8.
] [Full text]
Kelati A, Lagrange S, Le Duff F, Lacour JP, Passeron T. Treatment of elastosis perforans serpiginosa using a fractional carbon dioxide laser. JAMA Dermatol 2017;153:1063-4.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]