Facial Angioedema and Systemic Lupus Erythematosus: Case Report Daniel Bienstock, DMD, MD,* and Louis Mandel, DDSy Non-medication–related acquired deficiencies of C1 esterase inhibitor (C1-INH) can cause the facial acquired angioedema (AAE) seen in systemic lupus erythematosus (SLE). The defect can originate from a lymphoproliferative disease (LPD) that catabolizes C1-INH or from circulating antibodies that inactivate C1-INH. This report describes a third and rare variety of facial AAE originating in SLE in which there was no LPD or circulating antibodies to impede C1-INH activity. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 73:928-932, 2015 Angioedema (AE), a nonpitting, nonpruritic, nonerythematous, and nonpainful swelling, involves subcutaneous and submucosal tissues. It differs from urticaria in that urticarial swellings tend to be pruritic and involve the surface dermis. Sudden episodes of AE can occur in isolation or recurrently1,2 and often involve the face.2-6 A hereditary form of AE (HAE) results from a deficiency of the C1 esterase inhibitor (C1-INH) or its functional ability.1,7 With a faulty C1INH, a massive activation of the complement system results in increased vascular permeability and fluid escape stemming from stimulation of the kallikreinbradykinin pathway1,7-10 (Fig 1). Acquired forms of AE (AAE) also exist and can be differentiated from HAE in that they occur later in life and no family history is present.2,7,9 One variety of AAE derives its origin from antihypertensive medications, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, which also are associated with kinin-instigated AE,1,2,11 but are not related to C1-INH inadequacies. In addition, oral contraceptives and nonsteroidal anti-inflammatory drugs are occasionally associated with kinin-initiated AE. Acquired deficiencies in C1-INH also develop and incite AAE symptomatology. As with HAE, the inadequacies of C1-INH cause complement pathway activation and complement consumption. Activation of the complement system leads to bradykinin generation, increased vascular permeability, and clinical AE.10 This AAE category can originate from an association
with lymphoproliferative diseases (LPDs), which are thought to catabolize the C1-INH for unknown reasons,1-3,7,9,10,12,13 or the AAE might even be derived from the presence of antibodies that inactivate the C1-INH. This antibody inhibition of C1-INH has been reported in patients with systemic lupus erythematosus (SLE).1-4,7,9,12-16 A third type of AAE, linked to C1-INH, also seen in patients with SLE, has recently been reported in detail.1,3 These patients present with a low C1-INH that is only transient, hypocomplementemia (low C3, C4), increased immunoglobulin G (IgG), and absences of C1-INH antibodies and LPD. They also exhibit AE resolution at normalization of complement levels and C1-INH after immunosuppressive therapy. SLE clinical activity during the acute manifestation of AE is not observed. Clinical reports of AAE in patients with SLE have been published infrequently in the medical literature and have not been reported, as far as the authors could determine, in dental publications. The authors wish to alert the dental profession to the existence of facial AAE in patients with SLE in this case report. This case is very unusual in that it represents a rarely reported example of the third category of AAE.
Report of Case A 25-year-old female patient was seen in the emergency room of Columbia Presbyterian Medical Center
*Resident, Department of Oral and Maxillofacial Surgery, New
Address correspondence and reprint requests to Dr Mandel:
York-Presbyterian Medical Center (Columbia Campus), New York,
Columbia University College of Dental Medicine, 630 West 168th
NY.
Street, New York, NY 10032; e-mail: [email protected] Received October 3 2014 Accepted December 3 2014
yDirector, Salivary Gland Center; Associate Dean and Clinical Professor,
Department
of
Oral
and
Maxillofacial
Surgery,
Columbia University College of Dental Medicine, New York-
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Presbyterian Medical Center (Columbia Campus), New York,
0278-2391/14/01797-2
NY.
http://dx.doi.org/10.1016/j.joms.2014.12.007
928
929
BIENSTOCK AND MANDEL
FIGURE 1. Complement and kinin systems. Increased vascular permeability to fluid extravasation and thus edema are effects of the complement and kinin cascade systems. C1 esterase inhibitor blocks the effects of the steps displayed. Thus, deficiency in or inhibition of C1 esterase inhibitor leads to activation of the 2 systems. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
(New York, NY) with her first episode of bilateral facial swelling (Fig 2). The swelling had developed during the previous 24 hours. She also noted moderate swellings of her extremities. Six months previously, she was diagnosed with SLE at another institution. The diagnosis was based on the presence of polyarthralgia with some joint swellings, leukopenia, discoid skin lesions, malar rash, and positive IgG, antinuclear anti-
FIGURE 2. Facial swelling at time of hospital admission. Malar rash and discoid lesions are present. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
body (ANA), and anti-Smith antibody levels.17 Prednisone (10 mg) and hydrochloroquine (400 mg) were prescribed, but the patient discontinued their use several weeks before this visit. There was no associated clinical evidence of LPD. The SLE was clinically under control, but because of the acute facial swelling and a fever (100 F), the patient was hospitalized. Daily administrations of prednisone (40 mg) and hydrochloroquine (400 mg) were instituted. At admission, serologic studies showed a hypocomplementemia with low C3 (60.1 mg/dL; normal, 88 to 206 mg/dL), low C4 (10.8 mg/dL; normal, 13 to 75 mg/dL), and low total complement (40 CAE units; normal, 60 to 144 CAE units). In addition, the ANA titer and the anti-Smith antibody were positive and a leukopenia (1.4 109/L) was present. Unfortunately, C1-INH and anti–C1-INH levels were not ascertained at the time of admission. Magnetic resonance imaging (MRI) was ordered, and because the facial swelling involved the soft tissues around the locations of the 2 parotid glands, consultation with the Salivary Gland Center (SGC) was requested. Clinical examination in the SGC showed startling facial swelling that involved the parotid, masseteric, and buccal areas bilaterally. The swelling was not erythematous and was not pruritic. When palpated, it was noted to be soft, painless, and nonpitting.
930 Discoid skin lesions and a malar rash were evident facially (Fig 2). Intraorally, the mucosa was normal in appearance and normally moist. When the parotid glands were aggressively massaged extraorally, the salivary flow observed intraorally at the right and left parotid duct orifices was deemed to be normal in quality and quantity. Moderate asymptomatic soft swellings of the extremities also were noted. Fine-needle aspiration biopsy examination of the left parotid gland served to confirm the absence of a LPD. Scant benign acinar and ductal epithelial cells and no malignant cells were seen. MRI depicted a marked fluid infiltration of the facial subcutaneous tissues overlying the parotid glands and masseteric muscles bilaterally (Fig 3). The buccal areas also showed signs of considerable edematous involvement. In addition, the 2 parotid glands exhibited some fluid enhancement from contained saliva. The SGC made a diagnosis of AAE in a patient with SLE. Hospitalization and medications (prednisone and hydrochloroquine) were maintained for 7 days. Within this period, the fever subsided and the swellings of the face and extremities disappeared (Fig 4). The patient was discharged and is being followed in the rheumatology and dermatology clinics. Her prescribed medications include prednisone 60 mg and hydrochloroquine 400 mg. Serologic studies performed 6 weeks after hospitalization showed normal total complement levels (77 CAE units). Belatedly, the C1-INH level was requested and found to be 30 mg/dL (normal, 2l to 39 mg/dL). Its functional level also was normal. Of great importance is that the serology showed the absence of the autoantibody to C1-INH.
Discussion SLE is a heterogeneous autoimmune multiorgan disease characterized by different clinical manifestations and a wide profile of autoantibodies.17 It occurs in approximately 70 per 100,000 people with a 6 to 10 times increased frequency in women.18 The Systemic Lupus International Collaborating Clinics have proposed the currently accepted criteria for SLE diagnosis.17,19 The range of SLE diagnostic signs includes conditions, such as cutaneous rashes and arthritis, but extends to the more severe manifestations of glomerulonephritis, serositis, and hematologic and neurologic disorders.17,18 Irreversible organ damage is the end result. At the time of admission, the present patient’s previous diagnosis of SLE was clinically confirmed. The presence of arthritis, leukopenia, malar and discoid rashes, increased IgG, and positive ANA and anti-Smith levels were sufficient to authenticate the diagnosis of SLE.17,19
ANGIOEDEMA AND SYSTEMIC LUPUS ERYTHEMATOSUS
The discoid LE (DLE) seen in the present patient is a chronic dermatologic disease at the benign end of LE. Approximately 1 to 5% of patients with DLE progress to SLE and 25% of patients with SLE will develop DLE in the course of their disease.20 The complement system is concerned with defense against infection through its orchestration of opsonization, leukocyte activity, and bacterial lysis.16,21 It also functions to regulate B-cell activity and in the removal of apoptic cells and immune complexes.16,21 Complement contributes to the pathogenesis of SLE, and SLE is the most commonly seen autoimmune manifestation of complement deficiency.18,21 However, in general, the deficiency is not associated with increased SLE susceptibility. Apoptic cells serve as the major origin of autoantigens that drive the antibody response to SLE.18,21 The inadequate removal of apoptic cells in complement deficiency allows for autoantigens to interact with immune cells and leads to autoantibody formation of immune complexes with inflammatory tissue injury.21,22 The complement system plays a complex role in SLE development. It has a role in the inflammation that leads to the tissue and organ injury associated with SLE. Conversely, it also can have a protective action in that its deficiency leads to impaired clearance of immune complexes and apoptic cells.18,21 As stated earlier, a third type of AAE in LE has been described1,3 into which the present patient can be classified. The authors emphasize the fact that these patients present with a transient low C1-INH and a hypocomplementemia (low C3, C4). There is an absence of antibodies to C1-INH, no LPD, and no clinical SLE activity. Resolution of the AE and normalization of C3, C4, and C1-INH levels will occur with the administration of immunosuppressive therapy.1,3 The present case of AAE in a patient with SLE belongs to this third category of AAE in SLE.1,3 There was no clinical activity of the patient’s SLE during the acute AAE attack, and there was an absence of LPD, but hypocomplementemia was present. Major classic pathway-mediated complement consumption is not rare in patients with SLE.3,5 Why severe complement consumption develops in SLE and sets off AAE in this third category is unknown. Resolution of the AAE occurred and normalization of total serum complement developed with the immunosuppressive therapy. The C1-INH and its antibody levels were not measured at the initial hospital visit, but were found to be normal 6 weeks later. Transient low C1-INH functional and antigenic levels are inherent aspects of the third category of AAE.1,3 It was unfortunate that C1INH levels were not initially determined in this case, but the presumption can be made that its level was low at admission, albeit transient in nature. Nevertheless, the clinical and serologic studies, initially and after
BIENSTOCK AND MANDEL
931
FIGURE 3. A, T2-weighted fat-suppressed magnetic resonance image, axial view. Considerable subcutaneous edema is evident (circled). B, T2-weighted fat-suppressed magnetic resonance image, coronal view. Note the extensive edematous involvement of the subcutaneous tissues (E). Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
932
FIGURE 4. Normal facial contour 1 week after hospitalization. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
hospitalization, are consistent with placing the patient in the third group of patients with AAE and SLE. Their biologic manifestations of C1-INH deficiency characteristically are transient. In addition to subcutaneous tissue involvement, submucosal edema can develop. When it involves the airway, it can be life threatening.1-3,5,9,10 Complaints regarding abdominal pain result from intestinal mucosal edema.2,10 Besides prednisone therapy, the antifibrinolytic tranexamic acid,2,13 rituximab,1,2,4 and plasmapheresis2 have been therapeutically advocated and have met with some success. Because recurrent AE episodes are possible, long-term prophylaxis is needed.
References 1. Lahiri M, Lim AYN: Angioedema and systemic lupus erythematosus—A complementary association? Ann Acad Med Singapore 36:142, 2007 2. Furlanetto V Jr, Giassi Kde S, Neves Fde S, et al: Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus. Rev Bras Reumatol 50:102, 2010
ANGIOEDEMA AND SYSTEMIC LUPUS ERYTHEMATOSUS 3. Cacoub P, Fremeaux-Bacchi V, De Lacroix I, et al: A new type of acquired C1 inhibitor deficiency associated with lupus erythematosus. Arthritis Rheum 44:1836, 2001 4. Saigal K, Valencia IC, Cohen J, et al: Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: Rapid response to rituximab. J Am Acad Dermatol 49:5283, 2003 5. Ko C-H, Ng J, Kumar S, et al: Life-threatening angioedema in a patient with lupus. Clin Rheumatol 25:917, 2006 6. Anzai M, Maezawai R, Ohara T, et al: Systemic lupus erythematosus associated with facial edema, overproduction of interleukin5, and eosinophilia. J Clin Rheumatol 14:361, 2008 7. Nettis E, Colanardi MC, Loria MP, et al: Acquired C1-inhibitor deficiency in a patient with systemic lupus erythematosus: A case report and review of the literature. Eur J Clin Invest 35: 781, 2005 8. Cicardi M, Bisiani G, Cugno M, et al: Autoimmune C1 inhibitor deficiency: Report of eight patients. Am J Med 95:169, 1993 9. Pappalardo E, Zingale LC, Terlizzi A, et al: Mechanisms of C1-inhibitor deficiency. Immunobiology 205:542, 2002 10. Cugno M, Castelli R, Cicardi M: Angioedema due to acquired C1-inhibitor deficiency: A bridging condition between autoimmunity and lymphoproliferation. Autoimmun Rev 8:156, 2008 11. Seidman MD, Lewandowski CA, Sarpa JR, et al: Angioedema related angiotensin-converting enzyme inhibitors. Otolaryngol Head Neck Surg 102:727, 1990 12. Ordi-Rios J, Paredes J, Detarsio G, et al: Autoantibodies to C1 inhibitor in patients with lupus disease. J Rheumatol 24:1856, 1997 13. Carugati A, Pappalardo E, Zingale LC, et al: C1-inhibitor and angioedema. Mol Immunol 38:161, 2001 14. Nakamura S, Yoshinari M, Saku Y, et al: Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus affecting the central nervous system. Ann Rheum Dis 50:713, 1991 15. Ochonisky S, Intrator L, Wechsler J, et al: Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus. Dermatology 186:261, 1993 16. Meszaros T, Fust G, Farkas H, et al: C1-inhibitor autoantibodies in SLE. Lupus 19:634, 2010 17. Yu C, Gershwin ME, Chang C: Diagnostic criteria for systemic lupus erythematosus: A critical review. J Autoimmun 48-49:10, 2014 18. Leffler J, Bengtsson AA, Blom AM: The complement system in systemic lupus erythematosus: An update. Ann Rheum Dis 73: 1601, 2014 19. Petri M, Orbai AM, Alarcon GS, et al: Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677, 2012 20. Panjwani S: Early diagnosis and treatment of discoid lupus erythematosus. J Am Board Fam Med 22:206, 2009 21. Bryan AR, Wu EY: Complement deficiencies in systemic lupus erythematosus. Curr Allergy Asthma Rep 14:448, 2014 22. Walport MJ: Complement. Second of two parts. N Engl J Med 344:1140, 2001
with lymphoproliferative diseases (LPDs), which are thought to catabolize the C1-INH for unknown reasons,1-3,7,9,10,12,13 or the AAE might even be derived from the presence of antibodies that inactivate the C1-INH. This antibody inhibition of C1-INH has been reported in patients with systemic lupus erythematosus (SLE).1-4,7,9,12-16 A third type of AAE, linked to C1-INH, also seen in patients with SLE, has recently been reported in detail.1,3 These patients present with a low C1-INH that is only transient, hypocomplementemia (low C3, C4), increased immunoglobulin G (IgG), and absences of C1-INH antibodies and LPD. They also exhibit AE resolution at normalization of complement levels and C1-INH after immunosuppressive therapy. SLE clinical activity during the acute manifestation of AE is not observed. Clinical reports of AAE in patients with SLE have been published infrequently in the medical literature and have not been reported, as far as the authors could determine, in dental publications. The authors wish to alert the dental profession to the existence of facial AAE in patients with SLE in this case report. This case is very unusual in that it represents a rarely reported example of the third category of AAE.
Report of Case A 25-year-old female patient was seen in the emergency room of Columbia Presbyterian Medical Center
*Resident, Department of Oral and Maxillofacial Surgery, New
Address correspondence and reprint requests to Dr Mandel:
York-Presbyterian Medical Center (Columbia Campus), New York,
Columbia University College of Dental Medicine, 630 West 168th
NY.
Street, New York, NY 10032; e-mail: [email protected] Received October 3 2014 Accepted December 3 2014
yDirector, Salivary Gland Center; Associate Dean and Clinical Professor,
Department
of
Oral
and
Maxillofacial
Surgery,
Columbia University College of Dental Medicine, New York-
Ó 2015 American Association of Oral and Maxillofacial Surgeons
Presbyterian Medical Center (Columbia Campus), New York,
0278-2391/14/01797-2
NY.
http://dx.doi.org/10.1016/j.joms.2014.12.007
928
929
BIENSTOCK AND MANDEL
FIGURE 1. Complement and kinin systems. Increased vascular permeability to fluid extravasation and thus edema are effects of the complement and kinin cascade systems. C1 esterase inhibitor blocks the effects of the steps displayed. Thus, deficiency in or inhibition of C1 esterase inhibitor leads to activation of the 2 systems. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
(New York, NY) with her first episode of bilateral facial swelling (Fig 2). The swelling had developed during the previous 24 hours. She also noted moderate swellings of her extremities. Six months previously, she was diagnosed with SLE at another institution. The diagnosis was based on the presence of polyarthralgia with some joint swellings, leukopenia, discoid skin lesions, malar rash, and positive IgG, antinuclear anti-
FIGURE 2. Facial swelling at time of hospital admission. Malar rash and discoid lesions are present. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
body (ANA), and anti-Smith antibody levels.17 Prednisone (10 mg) and hydrochloroquine (400 mg) were prescribed, but the patient discontinued their use several weeks before this visit. There was no associated clinical evidence of LPD. The SLE was clinically under control, but because of the acute facial swelling and a fever (100 F), the patient was hospitalized. Daily administrations of prednisone (40 mg) and hydrochloroquine (400 mg) were instituted. At admission, serologic studies showed a hypocomplementemia with low C3 (60.1 mg/dL; normal, 88 to 206 mg/dL), low C4 (10.8 mg/dL; normal, 13 to 75 mg/dL), and low total complement (40 CAE units; normal, 60 to 144 CAE units). In addition, the ANA titer and the anti-Smith antibody were positive and a leukopenia (1.4 109/L) was present. Unfortunately, C1-INH and anti–C1-INH levels were not ascertained at the time of admission. Magnetic resonance imaging (MRI) was ordered, and because the facial swelling involved the soft tissues around the locations of the 2 parotid glands, consultation with the Salivary Gland Center (SGC) was requested. Clinical examination in the SGC showed startling facial swelling that involved the parotid, masseteric, and buccal areas bilaterally. The swelling was not erythematous and was not pruritic. When palpated, it was noted to be soft, painless, and nonpitting.
930 Discoid skin lesions and a malar rash were evident facially (Fig 2). Intraorally, the mucosa was normal in appearance and normally moist. When the parotid glands were aggressively massaged extraorally, the salivary flow observed intraorally at the right and left parotid duct orifices was deemed to be normal in quality and quantity. Moderate asymptomatic soft swellings of the extremities also were noted. Fine-needle aspiration biopsy examination of the left parotid gland served to confirm the absence of a LPD. Scant benign acinar and ductal epithelial cells and no malignant cells were seen. MRI depicted a marked fluid infiltration of the facial subcutaneous tissues overlying the parotid glands and masseteric muscles bilaterally (Fig 3). The buccal areas also showed signs of considerable edematous involvement. In addition, the 2 parotid glands exhibited some fluid enhancement from contained saliva. The SGC made a diagnosis of AAE in a patient with SLE. Hospitalization and medications (prednisone and hydrochloroquine) were maintained for 7 days. Within this period, the fever subsided and the swellings of the face and extremities disappeared (Fig 4). The patient was discharged and is being followed in the rheumatology and dermatology clinics. Her prescribed medications include prednisone 60 mg and hydrochloroquine 400 mg. Serologic studies performed 6 weeks after hospitalization showed normal total complement levels (77 CAE units). Belatedly, the C1-INH level was requested and found to be 30 mg/dL (normal, 2l to 39 mg/dL). Its functional level also was normal. Of great importance is that the serology showed the absence of the autoantibody to C1-INH.
Discussion SLE is a heterogeneous autoimmune multiorgan disease characterized by different clinical manifestations and a wide profile of autoantibodies.17 It occurs in approximately 70 per 100,000 people with a 6 to 10 times increased frequency in women.18 The Systemic Lupus International Collaborating Clinics have proposed the currently accepted criteria for SLE diagnosis.17,19 The range of SLE diagnostic signs includes conditions, such as cutaneous rashes and arthritis, but extends to the more severe manifestations of glomerulonephritis, serositis, and hematologic and neurologic disorders.17,18 Irreversible organ damage is the end result. At the time of admission, the present patient’s previous diagnosis of SLE was clinically confirmed. The presence of arthritis, leukopenia, malar and discoid rashes, increased IgG, and positive ANA and anti-Smith levels were sufficient to authenticate the diagnosis of SLE.17,19
ANGIOEDEMA AND SYSTEMIC LUPUS ERYTHEMATOSUS
The discoid LE (DLE) seen in the present patient is a chronic dermatologic disease at the benign end of LE. Approximately 1 to 5% of patients with DLE progress to SLE and 25% of patients with SLE will develop DLE in the course of their disease.20 The complement system is concerned with defense against infection through its orchestration of opsonization, leukocyte activity, and bacterial lysis.16,21 It also functions to regulate B-cell activity and in the removal of apoptic cells and immune complexes.16,21 Complement contributes to the pathogenesis of SLE, and SLE is the most commonly seen autoimmune manifestation of complement deficiency.18,21 However, in general, the deficiency is not associated with increased SLE susceptibility. Apoptic cells serve as the major origin of autoantigens that drive the antibody response to SLE.18,21 The inadequate removal of apoptic cells in complement deficiency allows for autoantigens to interact with immune cells and leads to autoantibody formation of immune complexes with inflammatory tissue injury.21,22 The complement system plays a complex role in SLE development. It has a role in the inflammation that leads to the tissue and organ injury associated with SLE. Conversely, it also can have a protective action in that its deficiency leads to impaired clearance of immune complexes and apoptic cells.18,21 As stated earlier, a third type of AAE in LE has been described1,3 into which the present patient can be classified. The authors emphasize the fact that these patients present with a transient low C1-INH and a hypocomplementemia (low C3, C4). There is an absence of antibodies to C1-INH, no LPD, and no clinical SLE activity. Resolution of the AE and normalization of C3, C4, and C1-INH levels will occur with the administration of immunosuppressive therapy.1,3 The present case of AAE in a patient with SLE belongs to this third category of AAE in SLE.1,3 There was no clinical activity of the patient’s SLE during the acute AAE attack, and there was an absence of LPD, but hypocomplementemia was present. Major classic pathway-mediated complement consumption is not rare in patients with SLE.3,5 Why severe complement consumption develops in SLE and sets off AAE in this third category is unknown. Resolution of the AAE occurred and normalization of total serum complement developed with the immunosuppressive therapy. The C1-INH and its antibody levels were not measured at the initial hospital visit, but were found to be normal 6 weeks later. Transient low C1-INH functional and antigenic levels are inherent aspects of the third category of AAE.1,3 It was unfortunate that C1INH levels were not initially determined in this case, but the presumption can be made that its level was low at admission, albeit transient in nature. Nevertheless, the clinical and serologic studies, initially and after
BIENSTOCK AND MANDEL
931
FIGURE 3. A, T2-weighted fat-suppressed magnetic resonance image, axial view. Considerable subcutaneous edema is evident (circled). B, T2-weighted fat-suppressed magnetic resonance image, coronal view. Note the extensive edematous involvement of the subcutaneous tissues (E). Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
932
FIGURE 4. Normal facial contour 1 week after hospitalization. Bienstock and Mandel. Angioedema and Systemic Lupus Erythematosus. J Oral Maxillofac Surg 2015.
hospitalization, are consistent with placing the patient in the third group of patients with AAE and SLE. Their biologic manifestations of C1-INH deficiency characteristically are transient. In addition to subcutaneous tissue involvement, submucosal edema can develop. When it involves the airway, it can be life threatening.1-3,5,9,10 Complaints regarding abdominal pain result from intestinal mucosal edema.2,10 Besides prednisone therapy, the antifibrinolytic tranexamic acid,2,13 rituximab,1,2,4 and plasmapheresis2 have been therapeutically advocated and have met with some success. Because recurrent AE episodes are possible, long-term prophylaxis is needed.
References 1. Lahiri M, Lim AYN: Angioedema and systemic lupus erythematosus—A complementary association? Ann Acad Med Singapore 36:142, 2007 2. Furlanetto V Jr, Giassi Kde S, Neves Fde S, et al: Intractable acquired autoimmune angioedema in a patient with systemic lupus erythematosus. Rev Bras Reumatol 50:102, 2010
ANGIOEDEMA AND SYSTEMIC LUPUS ERYTHEMATOSUS 3. Cacoub P, Fremeaux-Bacchi V, De Lacroix I, et al: A new type of acquired C1 inhibitor deficiency associated with lupus erythematosus. Arthritis Rheum 44:1836, 2001 4. Saigal K, Valencia IC, Cohen J, et al: Hypocomplementemic urticarial vasculitis with angioedema, a rare presentation of systemic lupus erythematosus: Rapid response to rituximab. J Am Acad Dermatol 49:5283, 2003 5. Ko C-H, Ng J, Kumar S, et al: Life-threatening angioedema in a patient with lupus. Clin Rheumatol 25:917, 2006 6. Anzai M, Maezawai R, Ohara T, et al: Systemic lupus erythematosus associated with facial edema, overproduction of interleukin5, and eosinophilia. J Clin Rheumatol 14:361, 2008 7. Nettis E, Colanardi MC, Loria MP, et al: Acquired C1-inhibitor deficiency in a patient with systemic lupus erythematosus: A case report and review of the literature. Eur J Clin Invest 35: 781, 2005 8. Cicardi M, Bisiani G, Cugno M, et al: Autoimmune C1 inhibitor deficiency: Report of eight patients. Am J Med 95:169, 1993 9. Pappalardo E, Zingale LC, Terlizzi A, et al: Mechanisms of C1-inhibitor deficiency. Immunobiology 205:542, 2002 10. Cugno M, Castelli R, Cicardi M: Angioedema due to acquired C1-inhibitor deficiency: A bridging condition between autoimmunity and lymphoproliferation. Autoimmun Rev 8:156, 2008 11. Seidman MD, Lewandowski CA, Sarpa JR, et al: Angioedema related angiotensin-converting enzyme inhibitors. Otolaryngol Head Neck Surg 102:727, 1990 12. Ordi-Rios J, Paredes J, Detarsio G, et al: Autoantibodies to C1 inhibitor in patients with lupus disease. J Rheumatol 24:1856, 1997 13. Carugati A, Pappalardo E, Zingale LC, et al: C1-inhibitor and angioedema. Mol Immunol 38:161, 2001 14. Nakamura S, Yoshinari M, Saku Y, et al: Acquired C1 inhibitor deficiency associated with systemic lupus erythematosus affecting the central nervous system. Ann Rheum Dis 50:713, 1991 15. Ochonisky S, Intrator L, Wechsler J, et al: Acquired C1 inhibitor deficiency revealing systemic lupus erythematosus. Dermatology 186:261, 1993 16. Meszaros T, Fust G, Farkas H, et al: C1-inhibitor autoantibodies in SLE. Lupus 19:634, 2010 17. Yu C, Gershwin ME, Chang C: Diagnostic criteria for systemic lupus erythematosus: A critical review. J Autoimmun 48-49:10, 2014 18. Leffler J, Bengtsson AA, Blom AM: The complement system in systemic lupus erythematosus: An update. Ann Rheum Dis 73: 1601, 2014 19. Petri M, Orbai AM, Alarcon GS, et al: Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677, 2012 20. Panjwani S: Early diagnosis and treatment of discoid lupus erythematosus. J Am Board Fam Med 22:206, 2009 21. Bryan AR, Wu EY: Complement deficiencies in systemic lupus erythematosus. Curr Allergy Asthma Rep 14:448, 2014 22. Walport MJ: Complement. Second of two parts. N Engl J Med 344:1140, 2001
