|CASE BASED REVIEW
|Ahead of print publication
TEN in a Case of SLE - A case based review
Shekhar Neema1, Sehdev Singh2, Abhishek Kumar3, S Radhakrishnan1
1 Department of Dermatology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Dermatology, Command Hospital (EC), Kolkata, West Bengal, India
3 Department of Rheumatology, Command Hospital (EC), Kolkata, West Bengal, India
Armed Forces Medical College, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Cutaneous manifestations in SLE are common, results in significant morbidity and helpful in diagnosis of underlying systemic disease. Vesiculobullous lesions in SLE are uncommon but present a diagnostic challenge. It can be a manifestation of SLE-specific or nonspecific pathology. It can also result from unrelated etiology such as drug-induced toxic epidermal necrolysis (TEN). Clinically, it is challenging to differentiate TEN-like acute cutaneous lupus erythematosus from classical TEN. We hereby present a case of TEN in SLE and discuss approach to vesiculobullous lesions in SLE.
Keywords: Acute cutaneous lupus erythematosus, systemic lupus erythematosus, toxic epidermal necrolysis
| Introduction|| |
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with myriad cutaneous manifestations. Skin is the second most commonly affected organ in SLE after joints. The spectrum of cutaneous findings in SLE has been classified into specific or nonspecific manifestations depending on classical histopathological features: vacuolization and necrosis of basal keratinocytes, basement membrane thickening, pigment incontinence, and lymphocytic infiltrate at the dermo-epidermal junction. The specific features of cutaneous lupus erythematosus (CLE) have been classified as acute CLE (ACLE), subacute CLE (SCLE), and chronic CLE (CCLE)., These manifestations differ from each other depending on clinical features and their association with SLE. ACLE can present as localized malar rash or generalized rash on photo-exposed area. It generally heals without scarring and is associated with SLE in most of the cases. SCLE presents as papulosquamous or annular morphology in photo-exposed area and associated with SLE in almost 50% cases. CCLE is also known as discoid lupus erythematosus (LE) and is the most scarring form of CLE. It presents with discoid lesions, mainly on the head-and-neck area, and localized DLE is associated with SLE in 5% cases, whereas in disseminated DLE, the risk is higher.,
Bullous lesions are rare cutaneous manifestations of SLE with a wide range of differential diagnosis. It includes bullous SLE, Rowell's syndrome, toxic epidermal necrolysis (TEN), and TEN-like ACLE. Clinically, it is difficult to differentiate these conditions from one another. We hereby present a case of classical TEN in a known case of SLE, which caused a diagnostic dilemma in management.
| Case Report|| |
A 29-year-old male presented with complaints of red-raised lesions over the body and oral ulcers of 10-day duration. Over the next 1 week, red-raised lesions became fluid-filled, leading to sheet-like detachment of skin. He also complained of difficulty swallowing and redness of eyes. There was a history of excessive sun exposure 1 week before the development of rash as he was working as an attendant in the school bus. He was diagnosed as a case of SLE with lupus nephritis when he presented with fever and joint pains to rheumatologist 3 months ago. Antinuclear antibodies (indirect immunofluorescence, titer 1:640) and anti-double-stranded DNA (indirect immunofluorescence) were positive, urine examination revealed subnephrotic-range proteinuria, and renal biopsy confirmed the diagnosis of Stage 2 lupus nephritis. He was started on prednisolone 30 mg once a day, mycophenolate mofetil 1.5 g twice a day, and hydroxychloroquine (HCQ) 100 mg twice a day.
General examination revealed pulse rate: 110/min, temperature: 100°F, respiratory rate: 20/min, and blood pressure: 110/82 mm Hg. Dermatological examination revealed involvement of the face and trunk with multiple, polysized, discrete to confluent vesicles and bulla, with relative sparing of photoprotected areas of upper eyelids and posterior auricular areas. Hemorrhagic crusting presents over lips and lesions over the face [Figure 1] and [Figure 2]. Investigations revealed hemoglobin: 10.5 g/dL, total leukocyte count: 3400/mm3, platelet: 2.2 lakh/mm3, ESR: 14 mm fall, blood urea nitrogen: 18 mg/dl, serum creatinine: 0.7 mg/dl, 24-h urinary protein: 292 mg, C3: 97.8 mg/dL (90–80), and C4: 19.9 mg/dL (10–40). Rest of the investigations including liver function tests, blood and urine culture, chest radiograph posteroanterior view, and ultrasound abdomen were within the normal limits. Histopathology of skin revealed epidermal necrosis, basal vacuolation, and subepidermal separation [Figure 3]. Because of the above clinical features, differential diagnosis of acute cutaneous lupus flare that is TEN-like ACLE and classical TEN was kept. Due to the presence of hemorrhagic crusting of lips, suggestive histopathology, normal complement level, and ESR, the diagnosis of TEN was considered first. HCQ was stopped and prednisolone increased to 60 mg once a day. Supportive therapy in the form of fluid and electrolyte balance, nutrition, care of oral cavity, normal saline compress for crust, and nano-silver dressings were done for eroded areas. The patient recovered in 2 weeks, the steroid was tapered, and the patient was discharged with advice not to start HCQ and use strict photoprotection [Figure 4].
|Figure 1: Facial edema, hemorrhagic crusting over lips, bullous lesions, and crusting involving almost entire face|
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|Figure 2: Involvement of the trunk and upper extremities with relative sparing of photoprotected area of the inner arm with flaccid vesicles and bullae|
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|Figure 3: Histopathology of skin biopsy shows subepidermal separation, basal vacuolation, and epidermal necrosis (H and E ×10)|
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| Discussion|| |
Vesiculobullous eruption in the presence of SLE presents a diagnostic challenge. It can result from SLE-specific immune pathology; however, unrelated conditions such as drug-induced TEN, dermatitis herpetiformis, epidermolysis bullosa acquisita, and transfusion-associated graft-versus-host disease can also manifest in the presence of SLE albeit rare. Bullous eruption in the presence of SLE is lumped in the broad group of bullous SLE, and this is incorrect as bullous SLE is a specific eruption with tense, subepidermal blisters, and the presence of neutrophils in dermal papillae. TEN-like eruption (sheet-like separation of skin) can involve preexisting acute or subacute cutaneous lupus lesion or occur de novo on unaffected skin.
Vesiculobullous skin disease in the presence of SLE can be classified as specific or nonspecific depending on histopathological features as (a) TEN-like ACLE – sheet-like cleavage of skin on preexisting ACLE lesions; (b) TEN-like SCLE – cleavage of skin on preexisting annular or psoriasiform SCLE lesions; (c) TEN-like lesions without any preexisting skin lesions; (d) vesiculobullous annular SCLE – bullous lesions at advancing edge of annular lesions; and (e) vesiculobullous chronic cutaneous LE – bullous lesions occurring in discoid lupus lesions. LE-nonspecific vesiculobullous lesions can occur due to other causes which are seen more commonly in SLE but have distinctive histopathology. Examples are dermatitis herpetiformis, epidermolysis bullosa acquisita, bullous pemphigoid-like vesiculobullous LE, and porphyria cutanea tarda.
Apart from LE-associated vesiculobullous disorders, these patients can develop unrelated diseases such as drug-induced TEN, acute graft-versus-host disease, and pseudoporphyria. Ting et al. proposed unifying designation acute syndrome of apoptotic pan-epidermolysis (ASAP) for acute and massive cleavage of the epidermis occurring due to apoptotic injury of any cause. It is an important concept as it allows early diagnosis and rapid treatment.
It is difficult to differentiate TEN-like LE from classical TEN. It is suggested that TEN-like LE has less severe mucosal involvement as compared to classical TEN. Patients with classical TEN have a history of taking incriminating drugs; however, patients with SLE are generally on multiple drugs, and a history of a specific drug may not be forthcoming. Serological tests such as anti-dsDNA, complement levels, and ESR are associated with acute lupus flare, particularly lupus nephritis, but their value in differentiating cutaneous flare or TEN-like ACLE from classical TEN is not known. Callaly et al. described HCQ-associated photo-induced TEN in a patient who was on long-term HCQ and developed classical TEN-like lesions on sun exposure. Our patient had a similar history: HCQ for 2 months, recent sun exposure, consistent clinical features, and histopathological findings. In view of these findings, we believe that our patient developed classical TEN which was induced due to TEN and we managed him by stopping HCQ and prednisolone. He did not develop any recurrence of the lesion even after 1 year of regular follow-up.
| Conclusion|| |
We present a case of HCQ-induced TEN. Vesiculobullous lesions in the presence of SLE pose a diagnostic challenge. A unifying concept of ASAP is useful in diagnosis but not very helpful in treatment, as the diagnosis of classical TEN requires identification and stopping of incriminating drugs to prevent immunological assault on the epidermis. We need immunological markers to identify various phenomena, as the clinical response of skin to apoptotic injury remains the same and may not help us beyond a certain point.
The authors have taken necessary consent from the patient for publication of his photograph.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]