|Year : 2019 | Volume
| Issue : 4 | Page : 209-212
Eruptive melanocytic nevi after toxic epidermal necrolysis: A case report and literature review
Yu-Wen Tsao1, Yu-Hung Wu2
1 Department of Medicine, Mackay Memorial Hospital, New Taipei City, Taiwan
2 Department of Medicine, Mackay Memorial Hospital, New Taipei City; Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan
|Date of Submission||05-Jun-2018|
|Date of Decision||14-Dec-2018|
|Date of Acceptance||03-Jan-2019|
|Date of Web Publication||22-Nov-2019|
Dr. Yu-Hung Wu
Department of Dermatology, Mackay Memorial Hospital, 92, Sec. 2, Zhongshan North Road, Taipei 10449
Source of Support: None, Conflict of Interest: None
Eruptive melanocytic nevi (EMN), developing after severe bullous disease or adverse drug eruption, are rare. We report a case involving a 20-year-old female student who had an episode of toxic epidermal necrolysis. She developed EMN on her limbs and abdomen half a year after recovery. The nevi appeared rapidly over several months, eventually stabilizing over the ensuing 3 years. Dermoscopy showed regular pigmented networks, which were pathologically consistent with junctional nevus. Although most eruptive nevi were stable in number and morphology, there was one previous report of malignant transformation. Patients with this condition should thus be closely followed.
Keywords: Eruptive melanocytic nevi, junctional nevi, toxic epidermal necrolysis
|How to cite this article:|
Tsao YW, Wu YH. Eruptive melanocytic nevi after toxic epidermal necrolysis: A case report and literature review. Dermatol Sin 2019;37:209-12
| Introduction|| |
Eruptive melanocytic nevus (EMN) is a rare condition wherein scattered or clustered pigmented nevi develop in a short period after a major event that affects the skin. It was first described by Kopf et al. in 1977 as appearing after severe bullous disease associated with erythema multiforme major. This phenomenon was subsequently and sporadically found to be associated with some conditions, such as human immunodeficiency virus infection,, posttransplantation, chronic myelocytic leukemia, Addison's disease, and epidermolysis bullosa. Recently, it was also described in patients receiving certain medications, such as cyclosporin and biologics., Here, we present the clinical, dermoscopic, and pathological features of a patient having EMN after toxic epidermal necrolysis (TEN).
| Case Report|| |
A 20-year-old female college student had easy bleeding and prolonged menstruation for 1 month. The blood test showed pancytopenia (hemoglobin level, 10.4 g/dL; white blood cell count, 3400; and platelet count, 2000), positive antinuclear antibody (1:160), and positive antiplatelet antibody. The C3 and C4 levels were normal, and anti-ds-DNA, rheumatoid factor, and hepatitis B and C antibodies were negative. She was diagnosed with idiopathic thrombocytopenia, possibly associated with autoimmune disease. The following medications were prescribed to control the disease: prednisolone 30 mg daily, folic acid 5 mg daily, danazol 200 mg every other day, colchicine 0.5 mg daily, magnesium oxide 250 mg three times a day, and famotidine 20 mg daily.
The medications were given for 1 month, and suddenly, she developed high fever up to 39°C, followed by a skin rash after 2 days. The rash first occurred on the bilateral forearms and then extended to the trunk and face with blister formation, accompanied by conjunctivitis and mucositis of the lips and oral cavity [Figure 1]a-d]. A skin biopsy was performed and showed detached necrotic epidermis with subepidermal separation [Figure 1]e. There were interface changes featured by the basal keratinocyte vacuolization and the presence of many dyskeratotic cells in the epidermis. The direct immunofluorescence study demonstrated the presence of cytoid bodies, which were positive for IgA, IgG, and IgM in the epidermis that was compatible with interface dermatitis. The findings indicated erythema multiforme major. The vesicles that scattered over the rash soon developed into bullae and skin necrosis rapidly over a few days. The blisters and necrosis of the skin involved >40% of her body surface area by the 5th day, and the diagnosis of TEN was confirmed. All previous medications were discontinued. She was admitted in the burn center. Supportive therapy, a short-term course of intravenous systemic steroids, and antibiotics for Pseudomonas infection were administered. The chest X-ray result was normal without signs of pneumonia. Serum test demonstrated elevated herpes simplex virus-1 IgG but normal IgM level and negative herpes simplex virus-2 IgM and IgG. The serology test for Mycoplasma pneumoniae was not performed.
|Figure 1: The episode of toxic epidermal necrolysis. Numerous scattered or confluent bullae on the (a) face and (b) abdomen. There was (c) conjunctivitis. (d) Some target-like lesions were present. (e) The biopsy showed a detached and totally necrotic epidermis (H and E, ×40, ×200)|
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Her skin exhibited complete reepithelialization after the 3-week hospitalization, and she was discharged without sequelae. There was no recurrence of thrombocytopenia, and no medication was taken after the discharge. Reviewing her medications before the event, a few case reports have revealed that some medications were associated with Stevens–Johnson syndrome (SJS) or TEN, including danazol, colchicine, and famotidine. These three drugs were listed in the possible cause when evaluated with Naranjo score and algorithm of drug causality for epidermal necrolysis score and the scores were all the same. No re-challenge test was performed to confirm the offending drug because of the risk of recurrence of severe adverse reactions.
The regenerated skin was pinkish and thin without scar. Approximately half a year after the event, pigmented lesions developed suddenly on her trunk and kept growing for approximately a month, with the same morphology. She visited our clinic about 3 years after the event of TEN. On physical examination, there were multiple scattered or clustered asymptomatic 1–3 mm, light to dark-brown, hyperpigmented macules or papules that appeared over her abdomen, back, and left arm [Figure 2]a. On dermoscopic examination, most of the lesions presented with regular pigmented networks and indicated junctional activity [Figure 2]b. She underwent biopsy of one of the pigmented abdominal lesions. Histopathology showed melanocytic nests in the basal cell layer [Figure 2]c and d] and pigmented incontinence in the papillary dermis [Figure 2]e, indicating junctional nevus. The distribution of melanocytes was relatively normal, as demonstrated by melan-A and HMB-45 stains. No further therapy was performed for those nevi. The number of nevi remained stable after the 4-year follow-up.
|Figure 2: Eruptive melanocytic nevi. (a) Scattered and grouped brownish to blackish macules and papules appeared suddenly within 1 and 6 months after toxic epidermal necrolysis. (b) Dermoscopy showed pigmented networks in most lesions, indicating junctional activity of the melanocytes. (c) The skin biopsy showed melanocytic proliferation limited to the epidermis (H and E, ×40). (d) There were a few nests in the epidermis with basal hyperpigmentation (H and E, ×400), and (e) pigment incontinence in the papillary dermis (H and E, ×400)|
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| Discussion|| |
This case demonstrated the clinical course and dermoscopic and pathological features of EMN after TEN. After the first two cases reported by Kopf et al., there are only a few similar additional cases that occurred after SJS or TEN.,,,,, Most patients are children or young adults, aging from 8 to 33 years. The clinical features of these cases are summarized in [Table 1].
The onset of development of EMN after SJS/TEN ranged from 3 weeks to 3 years [Table 1]. They can appear rapidly or be accidentally found. The distribution of EMN may be localized,,, but most of them are widespread. An interesting presentation was the grouped and confluent nevi in the localized area, similar to that in our patient [Figure 2]a, which were different from common acquired nevi with sporadic appearance. The location of EMN may be different due to the previous event. They may appear on palms and soles only in drug- or immunosuppression-associated EMN,, but volar areas were rarely observed in EMN developing after SJS/TEN.
The merging of EMN into a large patch created an uneven color, irregular border, and large size and may mislead to the impression of melanoma. However, most pathologic diagnoses of EMN after SJS/TEN are junctional or compound nevi,,,,,, and only one dysplastic nevus was documented. Most EMN become stable in number and morphology after they cease to appear. In a case with a 38-year follow-up period, the distribution and number were the same. Nevertheless, it has been reported that melanoma in situ can occur in a patient who had EMN after chemotherapy.
If there is any suspicious change, dermoscopy is a good evaluation method. The dermoscopic findings of EMN follow the general rules of junctional or compound nevi, such as networks and globules., In our patient, however, in different colors, the nevi demonstrated a uniform network pattern, indicating that most of them have junctional components only.
The pathogenesis of EMN is still unclear.,,,,, In 2003, Lanschuetzer et al. hypothesized that the blister fluid in patients with epidermolysis bullosa may contain growth factors that might affect the proliferation or migration of melanocytes and result in EMN in epidermolysis bullosa. However, SJS/TEN is a transient event, and EMN may develop several months or years after the event, which cannot be explained by the theory.
The other possible cause is the activation of BRAF gene mutations. Human nevi often have BRAFV600E oncogenic mutations and senescence-like cell cycle arrest of those melanocytes. BRAF mutation has been detected in the EMN that developed in a patient after 6-mercaptopurine therapy. EMN have also been observed after the use of multikinase inhibitors, such as sorafenib and sunitinib, which may affect the RAF pathway and lead to melanocyte proliferation.,, However, the phenomenon was only observed in a few cases and cannot be totally explained.
This report provided the clinical presentation of EMN after SJS/TEN. It is important to recognize the phenomenon and follow these nevi carefully. Dermoscopy may be useful in observing the changes.
This study was approved by the Institutional Review Board of MacKay Memorial Hospital, IRB no. 17MMHIS110 obtained on August 31, 2017.
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
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[Figure 1], [Figure 2]