|ONLINE ONLY - CASE REPORT
|Year : 2022 | Volume
| Issue : 1 | Page : 54
An Unusual presentation of Bullous pemphigoid: A toxic epidermal necrolysis variant
Ravina Naik, Varadraj V Pai, Pankaj Shukla
Department of Dermatology, Venereology and Leprosy, Goa Medical College, Bambolim, Goa, India
|Date of Submission||20-Jul-2020|
|Date of Decision||06-Oct-2020|
|Date of Acceptance||23-Nov-2020|
|Date of Web Publication||25-Feb-2022|
Varadraj V Pai
Department of Dermatology, Venereology and Leprosy, Goa Medical College, Bambolim, Goa
Source of Support: None, Conflict of Interest: None
Bullous pemphigoid (BP) is a subepidermal blistering skin disease that usually occurs in the elderly population. Morphological patterns of BP are varied and include lesions such as prurigo, urticaria, dyshidrosiform eczema, vegetative, erosive, erythema annulare centrifugum, nodular, and can very rarely toxic epidermal necrolysis. Drug-induced or drug triggered BP must be suspected if the disease subsides or remits on withdrawal of the probable offending drug. Dipeptidyl peptidase 4 inhibitors, aldosterone antagonists, anticholinergics, and dopaminergic medication are the common drugs associated with BP.
Keywords: Bullous pemphigoid, drugs, toxic epidermal necrolysis
|How to cite this article:|
Naik R, Pai VV, Shukla P. An Unusual presentation of Bullous pemphigoid: A toxic epidermal necrolysis variant. Clin Dermatol Rev 2022;6:54
| Introduction|| |
Bullous pemphigoid (BP) is a subepidermal blistering disorder that usually occurs in the elderly population and is characterized by large tense blisters with immune-pathological findings of linear deposits of C3 and IgG at the basement membrane zone. Apart from the classic bullous type, BP has various morphological variants which can mimic a variety of clinical conditions. They may appear in up to 20% of patients, which include and not necessarily limited to lesions such as prurigo, urticaria, dyshidrosiform eczema, vegetative, erythrodermic, erosive, erythema annulare centrifugum, nodular, and very rarely toxic epidermal necrolysis.,, Drug-induced or drug triggered BP must be suspected if the disease subsides or remits on withdrawal of the probable offending drug.
| Case Report|| |
A 75-year-old female presented to the emergency department with erosive skin lesions over the buttocks, bilateral extremities, trunk, and the back of 8 days duration. The lesions initially started as fluid-filled blisters of 2 days duration, which ruptured spontaneously, leaving behind erosions with desquamating skin with little tendency to heal. There was no history of oral, genital, or ocular lesions. History revealed symptoms of generalized pruritus all over the body for 2 months, for which the patient was on herbal medication for the same duration. The patient was also on amlodipine and hydrochlorothiazide for hypertension of 1 year duration.
On examination, the patient was febrile with tachycardia while the other vitals were stable. Dermatological examination revealed the erosions over the bilateral upper limb, lower limb, abdomen, and back with >50% body surface involvement. Few bullae were noted and the pseudo-Nikolsky sign was positive. The perilesional skin was normal [Figure 1] and [Figure 2] Oral and ocular mucous membranes were spared. The genital examination was normal.
Laboratory investigations revealed a normal hematological, biochemical examination, electrocardiogram, and chest X-ray. Serological and malignancy workup did not reveal positive findings. A skin punch biopsy was obtained for histopathological examination and direct immunofluorescence.
A provisional clinical diagnosis of toxic epidermal necrolysis was made and the patient was started on intravenous fluids and parenteral cefoperazone plus sulbactam. On the 2nd day of admission, the patient was started on intravenous (IV) immunoglobulin at the dose of 2 g/kg given over 3 days and capsule cyclosporine at a dose of 4 mg/kg. Lesions were quiescent for 1 week without any features of healing and erythema persisted at the margin.
In the meantime, the skin biopsy showed subepidermal bulla containing amorphous material with neutrophils and mononuclear cells [Figure 3] The direct immunofluorescence showed the linear staining of the basement membrane zone with IgG and C3 [Figure 4].
|Figure 3: Sub-epidermal bulla containing amorphous material with neutrophils and lymphocytes H and E, 10X10|
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|Figure 4: DIF is direct immunofluorescence linear staining of the basement membrane zone with IgG and C3|
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The diagnosis was revised to BP. Oral cyclosporine was stopped and the patient was started on IV dexamethasone 8 mg and azathioprine 50 mg twice a day. The patient started showing improvement on the 6th day of initiating IV Steroids and azathioprine and completely recovered after 2 weeks [Figure 5]. For the past 1 year after this episode, the patient occasionally develops a solitary blister over the extremity, which heals spontaneously without any medication.
| Discussion|| |
The difference in the clinical and etiological aspects of bullous pemphigoid and Toxic epidermal necrolysis (TEN) is given in [Table 1]., Accurate diagnosis of bullous pemphigoid depends on laboratory investigations such as biopsy, direct immunofluorescence, and indirect immunofluorescence. Direct immunofluorescence has a sensitivity and specificity of 90.8% and 100% in the diagnosis of BP. In our patient, diagnosis of toxic epidermal necrolysis was made on a clinical basis of acute onset, history of prior medication, and peeling off >50% of body surface area, which was later disproved after biopsy and immunological analysis. Among the autoimmune bullous disorders, the conditions presenting as TEN have been reported in paraneoplastic pemphigus, pemphigus, and drug-induced bullous pemphigoid (DIBP).,,
|Table 1: The difference in the clinical and etiological aspects of bullous pemphigoid and TEN|
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A metaanalysis of DIBP has shown that dipeptidyl peptidase 4 inhibitors, aldosterone antagonist, anticholinergics, and dopaminergic medication are the more commonly associated drugs. Furthermore, reported are cases associated with furosemide, angiotensin-converting enzyme inhibitors, beta-blockers, penicillins, anti-tumor necrosis factor, and more recently pembrolizumab., The usual clinical features in DIBP are an early age of onset, positive nikolsky sign, lesions over a normal-appearing skin, target lesions on the palms and soles, and mucosal involvement. The histopathological features of DIBP are marked eosinophilic infiltration, intraepidermal bullae, necrotic keratinocytes, and rapid therapeutic response to oral corticosteroids. DIBP may present as an acute and self-limited condition which responds promptly when the inciting drug is withdrawn or it may also present as classic bullous pemphigoid of chronic duration, in which case a likely diagnosis of drug-triggered BP is suspected.
Although the exact mechanism of occurrence of drug-induced autoimmune bullous disease is unclear, the hypotheses proposed are as follows:
- Crossreactivity to a structurally similar drug in a sensitized individual, for example., Aromatic neuroleptic
- Immune dysregulation or reorganization, leading to the inactivation of endogenous regulatory processes. For example., immune checkpoint inhibitors or biologicals used in targeted therapy act not only on the specific target that is assigned to them but also act on such targets on the T-regulatory cells which are suppressive cells required to maintain immune homeostasis and avoidance of autoimmunity, resulting in loss of self-tolerance and autoimmune response,,
- Drug acting as haptens that bind to and modify protein molecules in the basement membrane
- Molecular mimicry where the drug is misidentified by the immune system resulting in a T-cell response.
Some of these hypotheses have similarity with Stevens–Johnson syndrome and toxic epidermal necrolysis, which may explain the occurrence of such lesions in our patient. In fact, few cases of TEN like bullous pemphigoid, have been reported with pembrolizumab. The association of herbal medication in causation of BP in our patient may appear to be coincidental and not plausible due to the presence of itch before the introduction of medication. Furthermore, the review of literature did not yield any such association with herbal medication. Hydrochlorothiazides and calcium channel blockers have been reported to induce DIBP, but since the patient was on these medications for more than a year, their association with BP in our case appears limited. However, considering the relatively acute onset of symptoms, positive nikolshy sign, extent of involvement, the above-mentioned mechanisms, a rapid response to steroids, and occasional self-limited lesion, our patient appears to be a case of drug-triggered bullous pemphigoid.
| Conclusion|| |
This case represents a very unusual presentation of bullous pemphigoid. It is important to differentiate BP from TEN at the earliest as the treatment, course, and prognosis may vary widely.
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], [Figure 3], [Figure 4], [Figure 5]