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  Table of Contents  
Year : 2020  |  Volume : 11  |  Issue : 4  |  Page : 607-611  

Complete remission in a patient with treatment refractory bullous pemphigoid after a single dose of omalizumab

1 Department of Dermatology, Venereology and Leprology, Dr. RML Hospital and PGIMER, New Delhi, India
2 Department of Pathology, Dr. RML Hospital and PGIMER, New Delhi, India

Date of Web Publication13-Jul-2020

Correspondence Address:
Kabir Sardana
Room No. 108, Dermatology OPD, Dr. RML Hospital & ABVIMS, Baba Kharak Singh Marg, New Delhi - 110 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/idoj.IDOJ_438_19

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Bullous pemphigoid (BP) is an autoimmune disorder known to be mediated by immunoglobulin G (IgG) autoantibodies. The role of immunoglobulin E (IgE) antibodies is being investigated as their presence has been described in severe cases. Herein, we report a patient of BP who was refractory to most conventional agents and developed hypotension after rituximab but achieved lasting remission after a single dose of the anti-IgE monoclonal antibody omalizumab.

Keywords: Bullous pemphigoid, immunoglobulin E, omalizumab, refractory

How to cite this article:
Sinha S, Agrawal D, Sardana K, Kulhari A, Malhotra P. Complete remission in a patient with treatment refractory bullous pemphigoid after a single dose of omalizumab. Indian Dermatol Online J 2020;11:607-11

How to cite this URL:
Sinha S, Agrawal D, Sardana K, Kulhari A, Malhotra P. Complete remission in a patient with treatment refractory bullous pemphigoid after a single dose of omalizumab. Indian Dermatol Online J [serial online] 2020 [cited 2020 Aug 5];11:607-11. Available from: http://www.idoj.in/text.asp?2020/11/4/607/289619

   Introduction Top

Bullous pemphigoid (BP) is an autoimmune disorder with urticarial lesions with/without tense blisters. While immunoglobulin G (IgG) autoantibodies are known to play a pathogenic role; recently, immunoglobulin E (IgE) antibodies have been reported both in serum and lesions, and this is a topic of research that is being translated to its applicability into therapeutic interventions. We report a patient of BP who was refractory to high dose steroids and immunosuppressants and could not tolerate rituximab, but successfully achieved lasting remission after a single dose of 450 mg of omalizumab.

   Case Report Top

A 44-year-old obese lady presented to the Dermatology outpatient department with a 3-month history of tense fluid-filled blisters all over the body. The blisters were preceded by extremely itchy raised weals. Prior to presentation, she had been treated with high-dose oral steroids and dapsone which had led to partial resolution but discontinuation was followed by rapid reappearance of lesions. She had also received one dose of rituximab (500 mg i.v.) but had developed severe hypotension during the infusion consequent to which rituximab had been discontinued.

She was grossly overweight (BMI 40.6) but had no other comorbidities. On muco-cutaneous examination, she had tense bullae some of which were hemorrhagic, mostly overlying urticarial plaques along with extensive erosions and excoriations, involving almost the entire body, especially trunk and thighs [Figure 1]a, [Figure 1]b, [Figure 1]c. There was an ulcer on the right buccal mucosa, while the other mucosae appeared normal.
Figure 1: Clinical photograph of patient of bullous pemphigoid after 2 weeks of steroids and azathioprine showing (a) extensive erosions, excoriations and bullae over the whole back, (b) Vesicles and large bullae and erosions on the thigh, and on (c) nape of neck

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The diagnosis of BP was confirmed on histopathology which showed subepidermal blister with dermal infiltrate of eosinophils [Figure 2]a. Direct immunofluorescence revealed linear staining with IgG (2+) along basement membrane at dermoepidermal junction [Figure 2]b. Both absolute eosinophil count (5500 cells/mm 3, normal <350) and serum IgE level (11,579 IU/ml, normal <64) were considerably high. Hypereosinophilic syndrome and hyper-IgE syndromes were ruled out on the basis of absence of any systemic (respiratory/gastrointestinal/neurologic or rheumatologic) symptoms. There was no history of recurrent upper or lower respiratory tract or skin infections or eczema prior to the onset of presenting lesions. Peripheral smear did not show blast cells, thus ruling out eosinophilic leukemia too. Stool examination for ova/cyst/occult blood, Pap smear, and mammography was all within normal limits. There was no evidence of hepatitis B, hepatitis C, or HIV infection. Cardiomegaly was seen on a chest radiograph and a 2-D echocardiograph showed mild concentric left ventricular hypertrophy with grade 2 diastolic dysfunction. Ultrasound abdomen revealed hepatomegaly with grade 2 fatty liver but no splenomegaly. Immunoglobulin M (IgM) and immunoglobulin A (IgA) levels were within normal limits. Serum vitamin B12 and vitamin D3 levels were both low.
Figure 2: (a) Histopathology showing subepidermal blister with dermal infiltrate of eosinophils (arrow) (H and E × 400), and, (b) direct immunofluorescence showing linear staining with IgG (2+) along basement membrane at dermoepidermal junction (FITC × 200)

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She was started on 80 mg prednisolone and potent topical steroids but she continued to develop approximately 50 new lesions daily. She was switched to i.v. dexamethasone 8 mg twice daily (=106 mg prednisolone) and azathioprine 150 mg was added. In spite of this she continued to develop 30 to 50 new lesions daily over the next 2 weeks and, in light of the poor disease control and extremely high serum IgE levels, we administered Omalizumab 450 mg subcutaneously, while dexamethasone 16 mg i.v. was continued. The patient had a dramatic response subsequent to which she developed only ten lesions the day after omalizumab and no new lesion thereafter [Figure 3]a, [Figure 3]b, [Figure 3]c. Dexamethasone was replaced by oral prednisolone 60 mg and azathioprine 150 mg was continued. The oral steroids were tapered off over the next 4 months. The serum IgE levels corroborated well with the clinical response – from 11579 IU/mL at baseline they decreased to 8500 IU/mL after 2 months, 5368 IU/mL after 6 months and 2344 after 8 months. The AEC fell dramatically from 5500 cells/cumm at baseline to 220 after 8 months.
Figure 3: Clinical photographs after administration of single dose of omalizumab showing healing erosions and no vesicles or bullae over (a) back, (b) thigh, and, (c) nape of neck

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The patient is under regular follow up on azathioprine 100 mg and shows no evidence of relapse after after 10 months. Notably, she developed extensive milia, especially on her face and dorsa of hands, which decreased on topical tazarotene [Figure 4]a and [Figure 4]b.
Figure 4: Clinical photograph showing milia over sites of healing of vesicles over (a) face and (b) dorsa of hands

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   Discussion Top

BP is an autoimmune blistering disorder characterized by IgG autoantibodies directed against the hemidesmosomal proteins BP180 and BP230. The presence of IgE autoantibodies against the transmembrane protein BP 180 has been reported in BP serum samples and is the focus of much research.[1],[2],[3] Recent models of the disease have demonstrated that BP IgE can replicate the early stages of BP lesion formation. Ishiura et al.showed that IgE anti-BP230 levels had a strong association with local eosinophil accumulation and that they may have a role in attracting eosinophils to the skin lesions.[2] High serum IgE levels are associated with more severe BP and thus IgE inhibition could prove to be a valuable therapeutic modality in such patients.[4],[5] Our case was a treatment refractory case and this was probably related to the high IgE and AEC levels.

Omalizumab is a humanized monoclonal antibody that inhibits IgE binding to its receptor FcεRI and is FDA approved for severe uncontrolled asthma. The use of this drug in BP is based on certain observations – serum IgE levels are elevated in most BP patients, IgE anti-BP230 antibodies are known to play a role in eosinophil accumulation and IgE levels and eosinophil counts have been known to mirror disease activity in BP.[2],[3],[4],[5] Free IgE levels are seen to decrease within hours of the first dose of omalizumab. There is a remarkable heterogeneity in dosimetry, with the doses varying from 100 mg to 525 mg subcutaneously at 2-8 weekly intervals for durations ranging from 2–20 months [Table 1]. Most authors use the asthma nomogram to decide the dose. This nomogram uses body weight and total IgE levels to determine the dose. Since both these parameters were very high in our patient, we gave a high first dose of 450 mg.
Table 1: Summary of published cases of bullous pemphigoid patients treated with omalizumab till date

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Remarkably, our patient achieved complete control with the single dose. This may be related to the extremely high IgE levels (>11000 IU/ml), hitherto unreported in any case of BP on omalizumab. While we did not repeat the dose due to monetary constraints, this was probably serendipitous as there was remarkable and lasting control with a single dose. We believe that possibly, there is a subset of patients, with pruritic urticarial lesions preceding the bullae, and very high IgE and/or AEC levels, which may not require repeated dosing with omalizumab to achieve disease control and may be eventually managed on conventional therapy alone. Further studies would be needed to clearly define this subset of patients but this could significantly decrease the cost of treatment.

To the best of our knowledge, a single dose of omalizumab leading to complete remission has not been reported as yet in BP. While we are unable to offer an explanation for the remarkable response with one dose, possibly omalizumab may be used as a form of “rescue therapy” in cases of treatment refractory BP.

   Conclusion Top

Omalizumab could prove to be a valuable reserve option for treatment refractory BP, especially in patients with very high IgE and/or AEC levels. Attempts should also be made to switch the patient to conventional modes of treatment once initial control is achieved to cut down treatment cost.

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 Top

van Beek N, Lüttmann N, Huebner F, Recke A, Karl I, Schulze FS, et al. Correlation of serum levels of IgE autoantibodies against BP180 with bullous pemphigoid disease activity. JAMA Dermatol 2017;153:30-8.  Back to cited text no. 1
Ishiura N1, Fujimoto M, Watanabe R, Nakashima H, Kuwano Y, Yazawa N, et al. Serum levels of IgE anti-BP180 and anti-BP230 autoantibodies in patients with bullous pemphigoid. J Dermatol Sci 2008;49:153-61.  Back to cited text no. 2
Hashimoto T, Ohzono A, Teye K, Numata S, Hiroyasu S, Tsuruta D, et al. Detection of IgE autoantibodies to BP180 and BP230 and their relationship to clinical features in bullous pemphigoid. Br J Dermatol 2017;177:141-51.  Back to cited text no. 3
Saniklidou AH, Tighe PJ, Fairclough LC, Todd I. IgE autoantibodies and their association with the disease activity and phenotype in bullous pemphigoid: A systematic review. Arch Dermatol Res 2018;310:11-28.  Back to cited text no. 4
Kwon HJ, Ahn GR, Choi SY, Li K, Seo SJ. Explosive bullous pemphigoid with high serum total IgE: Serum IgE as a biomarker that reflects disease activity. JAAD Case Rep 2018;4:352-4.  Back to cited text no. 5
Fairley JA, Baum CL, Brandt DS, Messingham KA. Pathogenicity of IgE in autoimmunity: Successful treatment of bullous pemphigoid with omalizumab. J Allergy Clin Immunol 2009;123:704-5.  Back to cited text no. 6
London VA, Kim GH, Fairley JA, Woodley DT. Successful treatment of bullous pemphigoid with omalizumab. Arch Dermatol 2012;148:1241-3.  Back to cited text no. 7
Dufour C, Souillet AL, Chaneliere C, Jouen F, Bodemer C, Jullien D, et al. Successful management of severe infant bullous pemphigoid with omalizumab. Br J Dermatol 2012;166:1140-2.  Back to cited text no. 8
Yu KK, Crew AB, Messingham KA, Fairley JA, Woodley DT. Omalizumab therapy for bullous pemphigoid. J Am Acad Dermatol 2014;71:468-74.  Back to cited text no. 9
Yalcin AD, Genc GE, Celik B, Gumuslu S. Anti-IgE monoclonal antibody (omalizumab) is effective in treating bullous pemphigoid and its effects on soluble CD200. Clin Lab 2014;60:523-4.  Back to cited text no. 10
Gönül M, Keseroglu HO, Ergin C, Özcan I, Erdem Ö. Bullous pemphigoid successfully treated with omalizumab. Indian J Dermatol Venereol Leprol 2016;82:577-9.  Back to cited text no. 11
Balakirski G, Alkhateeb A, Merk HF, Leverkus M, Megahed M. Successful treatment of bullous pemphigoid with omalizumab as corticosteroid-sparing agent: Report of two cases and review of literature. J Eur Acad Dermatol Venereol 2016;30:1778-82.  Back to cited text no. 12
Menzinger S, Kaya G, Schmidt E, Fontao L, Laffitte E. Biological and clinical response to omalizumab in a patient with bullous pemphigoid. Acta Dermato Venereol 2018;98:284-6.  Back to cited text no. 13
Uysal PI, Yalcin B, Oktem A. Our clinical experience with the use of omalizumab in the treatment of bullous pemphigoid. Turkderm Turk Arch Drematol Venereol 2017;51:124-8.  Back to cited text no. 14
Bilgiç Temel A, Bassorgun CI, Akman-Karakaş A, Alpsoy E, Uzun S. Successful treatment of a bullous pemphigoid patient with rituximab who was refractory to corticosteroid and omalizumab treatments. Case Rep Dermatol 2017;9:38-44.  Back to cited text no. 15
James T, Salman S, Stevenson B, Bundell C, Kelly G, Nolan D, et al. IgE blockade in autoimmunity: Omalizumab induced remission of bullous pemphigoid. Clin Immunol 2019;198:54-6.  Back to cited text no. 16
Vico-Alonso C, Calleja-Algarra A, Aragon-Miguel R, Sanchez-Velazquez A, Velasco-Tamariz V, Ortiz-Romero PL, et al. Omalizumab as an alternative therapeutic tool in the treatment of bullous pemphigoid: A case report. Dermatol Ther 2019:e12829.  Back to cited text no. 17


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

  [Table 1]


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