|Year : 2022 | Volume
| Issue : 1 | Page : 58-59
A case of bullous pemphigoid associated with plasma cell leukemia
Yu-Cheng Liang1, Wei-Ting Liu2, Cheng-Lin Wu3, Julia Yu-Yun Lee2, Chao-Chun Yang4
1 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
2 Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
3 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
4 Department of Dermatology, College of Medicine, National Cheng Kung University Hospital; International Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan, Taiwan
|Date of Submission||09-Aug-2021|
|Date of Decision||23-Jan-2022|
|Date of Acceptance||08-Feb-2022|
|Date of Web Publication||30-Mar-2022|
Dr. Chao-Chun Yang
Department of Dermatology, College of Medicine, National Cheng Kung University, No. 138, Shen-Li Road, Tainan 704
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Liang YC, Liu WT, Wu CL, Lee JY, Yang CC. A case of bullous pemphigoid associated with plasma cell leukemia. Dermatol Sin 2022;40:58-9
A 72-year-old woman presented to our department with a 1-month history of pruritic, annular plaques, with tense blisters on the trunk, neck, buttocks, and four extremities without mucosal involvement. The blisters were of varying size and with clear to hemorrhagic fluid. The Nikolsky sign was negative. A skin biopsy was obtained and showed a subepidermal cleft with a few eosinophils in the cleft or the dermoepidermal junction and a sparse lymphohistiocytic infiltrate in the papillary dermis [Figure 1]. The direct immunofluorescence revealed immunoglobulin G (IgG) and C3 granular staining along the roof of dermo-epidermal separation. The indirect immunofluorescence (IIF) showed circulating IgG binding to the basement membrane of normal human skin at a titer of 1:40. Anti-bullous pemphigoid (BP) 180 IgG was present in the serum (>200 RU/ml) by enzyme-linked immunosorbent assay. Taken together, the diagnosis of BP was favored.
|Figure 1: (a) There are multiple annular erythematous plaques on the trunk with the border studded with tense hemorrhagic vesicles. (b) The histopathology shows a subepidermal cleft formation with the presence of a few eosinophils (arrow) (H and E, ×100). (c and d) The direct immunofluorescence study reveals granular immunoglobulin G and C3 staining along the roof of the blister.|
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A routine laboratory blood workup revealed leukocytosis (33,900/μL) with the predominance of plasma cells (64.5%), normocytic anemia (Hemoglobin 8.9 g/dl, mean corpuscular volume 97.4fL), and hypercalcemia (10.5 mg/dl). Her renal function was normal. The serum immunoglobulin levels were normal by protein electrophoresis. The immunofixation electrophoresis of serum showed free kappa monoclonal gammopathy (free-kappa light chain: 2679 mg/dl and free kappa-lambda ratio: 450.25). The X-ray images showed multiple punch-out lesions in the skull and compression fracture of the L4 vertebra. The bone marrow studies showed increased plasma cells infiltration, accounting for more than 90% of all nucleated cells. Multiple myeloma (MM) with circulating plasma cells, also known as plasma cell leukemia (PCL), was diagnosed. The histopathology of the skin biopsy was reviewed again. No amyloid deposition or plasma cell surrounding the blister is noted.
Soon after the diagnosis, the patient was admitted to the hospital where intravenous methylprednisolone 20 mg twice daily (0.6 mg/kg/day) and oral doxycycline 100 mg twice daily were initiated for BP. The first dose of bortezomib, thalidomide, and dexamethasone (VTd therapy) for PCL was also administered. Her skin lesions improved gradually with dried-up blisters and less bullous formation, and plasma cells were not detected in the peripheral blood. However, flare-up of blisters on the trunk and extremities and increased plasma cell counts in the peripheral blood were noted when the dose of systemic corticosteroid was reduced. Oral azathioprine 50 mg daily was then added, followed by the second dose of VTd therapy, and the skin lesions and plasma cells in the peripheral blood were controlled again, as well as decreased free kappa light chain in the serum. The skin lesions completely resolved at the 4th month after 4 cycles of VTd therapy, in combination with prednisolone 20 mg and azathioprine 50 mg daily. By the 8th month after treatment, the skin lesions remained completely remitted and PCL was partially remitted under the use of azathioprine 50 mg daily without prednisolone and 9 cycles of VTd therapy.
MM and PCL are malignant proliferation of monoclonal plasma cells with the production of immunoglobulins or their fragments. MM had been associated with bullous diseases, including toxic epidermal necrolysis, erythema multiforme, and Grover's diseases, but to our knowledge, the association with BP had never been reported.
BP is an autoimmune subepidermal bullous disease with autoimmune antibodies against two hemidesmosomal proteins, BP180, and BP230, in the basement membrane zone (BMZ), resulting subepidermal blisters. BP affects elderly individuals in most cases. An elevated incidence of malignancy has been reported in patients with BP, comparing to the general population, ranging 5.8% –19%. A higher association was noticed in some specific malignancies, such as renal cancer, laryngeal cancer, and hematologic malignancies., BP associated with neoplasm (BPAN) shares common clinical features with ordinary BP, except higher incidence of negative IIF, mucosal involvement, and erythema gyratum repens-like features in BPAN.
Several hypotheses for the pathogenesis of BPAN have been postulated. First, the antibodies against malignancy antigens may cross-react with the BMZ. Second, the malignancy may produce substances that damage the BMZ, with secondary production of anti-basement membrane antibodies. Third, an external agent, such as virus, may generate the malignancy and damage the BMZ.,
In conclusion, we report a case of BP with subsequent diagnosis of PCL during blood workups. Both dermatologists and hematologists should be aware of this comorbidity and pertinent examination should be arranged if there is clinical suspicion.
This study was approved by the Institutional Review Board of National Cheng Kung University Hospital (approval number: B-EC-110-028.; approval date: 2021.08.06). The patient consent was waived by the IRB.
Financial support and sponsorship
Conflicts of interest
Prof. Chao-Chun Yang and Prof. Julia Yu-Yun Lee, editorial board members at Dermatologica Sinica, had no roles in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.
| References|| |
Bayer-Garner IB, Smoller BR. The spectrum of cutaneous disease in multiple myeloma. J Am Acad Dermatol 2003;48:497-507.
Balestri R, Magnano M, La Placa M, Patrizi A, Angileri L, Tengattini V, et al.
Malignancies in bullous pemphigoid: A controversial association. J Dermatol 2016;43:125-33.
Kartan S, Shi VY, Clark AK, Chan LS. Paraneoplastic pemphigus and autoimmune blistering diseases associated with neoplasm: Characteristics, diagnosis, associated neoplasms, proposed pathogenesis, treatment. Am J Clin Dermatol 2017;18:105-26.
Person JR, Rogers RS 3rd
. Bullous and cicatricial pemphigoid. Clinical, histopathologic, and immunopathologic correlations. Mayo Clin Proc 1977;52:54-66.
Hauschild A, Swensson O, Christophers E. Paraneoplastic bullous pemphigoid resembling erythema gyratum repens. Br J Dermatol 1999;140:550-2.