Patient Oriented Problem Solving (POPS) Case Report Giant cell arteritis presenting as facial swelling Anthony J. Ricketti, M.D.,* Dennis J. Cleri, M.D.,# Janusz J. Godyn, M.D.,§ Suzanne H. Shenk, D.O.,¶ and John R. Vernaleo, M.D.储 ABSTRACT Facial swelling is commonly ascribed to angioedema and a host of other causes. Temporal arteritis (TA), a disease most often diagnosed in patients over the age of 50 years, frequently presents with nonspecific and often ignored complaints (headache, symptoms of polymyalgia rheumatica, low-grade fever, fever of unknown origin, loss of appetite, depression, joint pains, weight loss, hair loss, and even respiratory symptoms). The diagnosis of TA is highly likely in the presence of new-onset headaches, polymyalgia rheumatica, and a tender, cord-like, or swollen temporal artery. Facial swelling must be appreciated as another presentation of TA, especially when accompanied by other nonspecific symptoms. High clinical suspicion, immediate treatment, and definitive diagnosis by temporal artery biopsy are necessary to prevent the most severe vascular complications of blindness and cerebrovascular accidents. Treatment with corticosteroids is most often successful. Because this treatment is fraught with all the risks of high-dose and prolonged steroid therapy, it should only be initiated in cases of significant clinical suspicion, followed by a timely temporal artery biopsy to confirm the diagnosis. Delay in therapy increases the risk of a vascular catastrophe. Delay in obtaining a temporal artery biopsy after therapy has been initiated decreases the diagnostic sensitivity of the test. Other modalities of immunosuppressive therapy remain either unsuccessful or unproven. Concomitant low-dose aspirin therapy appears to hold promise. (Allergy Asthma Proc 29:538 –550, 2008; doi: 10.2500/aap.2008.29.3161) Key words: Blindness, corticosteroid treatment, facial swelling, giant cell arteritis, jaw claudication, ophthalmoplegia, polymyalgia rheumatica, temporal arteritis, temporal artery biopsy CASE PRESENTATION Chief Complaint he patient is an 85-year-old white woman who presents with severe frontal headache, facial pain and swelling, and difficulty swallowing. T From the *Section of Allergy and Immunology, and #Internal Medicine Residency Program, St. Francis Medical Center, Trenton, New Jersey, and Seton Hall University School of Graduate Medical Education, South Orange, New Jersey, §Department of Pathology, UMDNJ–Robert Wood Johnson Medical School, RWJ University Hospital Hamilton, Hamilton, New Jersey, ¶Internal Medicine Residency, St. Francis Medical Center, Trenton, New Jersey, and 储Division of Infectious Diseases, Wyckoff Heights Medical Center, Brooklyn, New York There are no sources of support that require acknowledgment The authors have indicated there is no funding in support of this document. Additionally, there are no other relationships that might pose a conflict of interest by any of the authors. None of the authors has any professional or financial relationships relevant to the subject matter in this paper. This article and any tables or figures therein have not been submitted to or are under consideration by any other publisher or publication Address correspondence and reprint requests to Dennis J. Cleri, M.D., St. Francis Medical Center, Department of Medicine, Room B-158, 601 Hamilton Avenue, Trenton, NJ 08629-1986 E-mail address: dcleri@StFrancisMedical.org Copyright © 2008, OceanSide Publications, Inc., U.S.A. 538 History of Present Illness The patient presented with 3 days of severe frontal headache, facial pain and swelling, and difficulty swallowing. She noted fever to 101.6°F, neck pain, myalgias, weakness, and swelling of her tongue. Swelling of her face, eyelids, and tongue steadily progressed. One day before admission, she experienced nausea and several episodes of vomiting. The patient denied any prior episodes of chronic or severe headaches or angioedema. Over the next 24 hours, there was marked improvement in the facial swelling but no improvement in facial pain, neck pain, or swallowing and worsening of tenderness over the temporal areas. The patient denied any prior episodes of chronic or severe headaches, angioedema, or drug or food hypersensitivity. Physical Examination on Hospital Admission Vital signs were temperature, 101.6°F; heart rate, 93/ minute; respiratory rate, 18/minute; and a blood pressure of 150/80 mm Hg. Her face, eyelids and tongue were markedly swollen. The extraocular movements were intact, but the fundi could not be well visualized. Her head was tender in the temporal regions, but no cords were appreciated. Mild nuchal rigidity and ten- September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm derness and a thyroid goiter were noted. The remainder of the physical examination was normal. QUESTION 1 Which of the following are included in the differential diagnosis of a patient presenting with a painful face with or without swelling? A. Angioedema B. Submandibular calculi C. Infections of the submandibular gland D. Osteomyelitis E. Muscle contraction headaches F. Carotidynia G. Trigeminal neuralgia H. Giant cell (temporal) arteritis QUESTION 2 Which of the following are included in the differential diagnosis of giant cell (temporal) arteritis? A. Migraine headache B. Carotidynia C. Polymyalgia rheumatica (PMR) D. Rheumatoid arthritis E. Trigeminal neuralgia F. Temporomandibular joint disease G. Sinusitis H. Oral/dental pathology I. Autoimmune thyroid disease J. Occult malignancy K. Causes of sudden blindness Discussion of the Differential Diagnosis Causes of facial swelling include angioedema (chronic idiopathic, acquired, or hereditary angioedema), malignancy, allergic angioedema secondary to food or drug allergy, submandibular calculi or infections, osteomyelitis, Gleich syndrome, malignancy, and sinusitis.1,2 C1-esterase inhibitor autoantibodies have caused isolated tongue swelling.3 Angina, temporomandibular joint disease, muscle contraction headaches, carotidynia, trigeminal neuralgia, PMR, and temporal arteritis (TA) (giant cell arteritis [GCA], or cranial arteritis) comprise causes of facial pain. The differential diagnosis for TA/GCA includes all of the aforementioned, multiple myeloma, myalgias from statin therapy, osteoarthritis, rheumatoid arthritis, occult malignancy, and causes of sudden blindness.1,4,5 TA/GCA is the most common form of idiopathic large- and medium-sized vessel vasculitis of branches of the aortic arch.6 GCA has an incidence of 18 cases/ 100,000 in patients ⬎50 years of age.5 The disease affects all races but predominates in white people from Scandinavia, Great Britain, and the northern United States.7 In northern Europe the ratio of women to men is 3:1, and in Spain this ratio is lower.8,9 TA/GCA’s clinical picture includes new onset of headache (from temporal or occipital artery involvement), a tender and/or nodular temporal artery with decreased pulsation, elevated erythrocyte sedimentation rate (ESR), and a diagnostic temporal artery biopsy.1,5,6 Rarely, physical examination has revealed cordlike pulseless and thickened facial and occipital arteries.10 In an older study of 100 patients, the most common initial complaints were headache (60% of patients) and PMR (40 – 60% of patients).7,8,11–13 Five to 40% of patients with PMR have occult TA.14 Synovitis has been reported not infrequently, and arthralgia in the proximal joints is common.15,16 Respiratory symptoms are infrequent but not rare (9% incidence) and may be the presenting complaint in 4% of patients.1 Aortic regurgitation, myocardial infarction, and deafness are rare complications.17 It should be noted that a normal ESR is found in 5–24% of patients.1 Biopsies are diagnostic in 80 –95% of untreated patients.1 Steroids reduce their diagnostic value to 78% after ⬍2 weeks of therapy, 65% after 2– 4 weeks of therapy, and 40% after 4 or more weeks of therapy.18 However, most clinicians will start steroid therapy as soon as TA/GCA is suspected and quickly proceed with a temporal artery biopsy.16,19 Unilateral biopsies have a 4 –5% false-negative frequency.7,12,14 Bilateral temporal artery biopsies are mandatory. In one study, 14% of patients were diagnosed on the innocent-appearing side.20 Reactive bone marrows, leukocytosis, thrombocytosis, elevated liver enzymes, elevated C-reactive protein, and anemia of chronic disease are well documented in these patients.12,14,16,21 In typical cases, the superficial temporal artery will be readily visible, knotty, pulseless, tortuous, thickened, and tender. Hair loss and ischemic scalp ulceration have been reported. Similar findings have been reported in the contralateral upper extremity, neck, and chest arteries.1 One-half of the patients have eye complaints. Diplopia is caused by vasculitis affecting cranial nerves III, IV, and VI. Thirteen to 50% of untreated patients develop sudden onset of permanent blindness from occlusion of the posterior ciliary artery. Blindness in both eyes is rare. This is often preceded by amaurosis fugax or ophthalmoplegia.1,5–7 Significant involvement of large arteries (27% of patients) includes aortic aneurysms or dissection (18%), stenosis of the superior branches of the aortic arch especially the subclavian and axillary arteries (10 –15%), and, occasionally, stenosis of the lower aortic vessels (⬍1%). These patients have a 17-fold increased risk of thoracic aortic aneurysms and a 2.4-fold increased risk of abdominal aortic aneurysms. Symptoms related to these vessels include extremity and jaw claudication (34% of patients with TA) and diffuse mandibular, dental, and sinus pain or discomfort.5,6,14 Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm 539 Facial swelling has been infrequently reported as the initial presentation of TA/GCA.15,22,23 Scalp necrosis, tongue necrosis, other cranial neuropathies, peripheral neuropathies, cerebrovascular accidents, transient ischemic attacks, and cotton–wool exudates secondary to retinal ischemia have been reported. TA/GCA is a well-appreciated cause of fever of unknown origin, anorexia, weight loss, wasting syndrome, depression, headache, and failure to thrive.5,14,17 A review of 260 consecutive patients with TA/GCA found 17 patients (6.5%) with head-and-neck swelling. These authors report that facial swelling was often the initial manifestation of disease and transient. Facial swelling was often painful, involved the orbital region and face, especially the lower part of the cheeks and maxillae. The neck was less frequently involved, and rarely the tongue, limb, or forehead. Ear, nose, throat symptoms were observed in 80% of cases (jaw claudication and frank trismus). Two patients had permanent visual impairment and one patient had sudden hearing loss. The swelling either spontaneously disappeared or regressed after steroid therapy. A small number of patients suffered recurrence of their facial swelling.24,25 A variant of this presentation is hemifacial edema, trismus, and fever. These manifestations disappeared before more typical findings of TA/GCA led clinicians to the diagnosis.26 Facial swelling as a result of TA/GCA has preceded anterior ischemic optic neuropathy and is believed to be “an indicator” of anterior ischemic optic neuropathy.15 The mere sensation of facial puffiness may be an initial manifestation of TA/GCA and a predictor of visual disturbances.27 Another case of TA/GCA facial swelling was accompanied by glossitis and odynophagia (claudication-like symptoms of the tongue and muscles of deglutition).12 Even more unusual is TA/ GCA presenting as a submandibular mass as the result of facial artery involvement.22 Patients must meet three of the following five criteria to be accepted in studies for TA: age of ⬎50 years, new onset of headache (found in 65–75% of TA patients), abnormal temporal artery by physical examination, ESR of ⬎50 mm/hour, and diagnostic temporal artery biopsy. An ESR of ⬍50 mm/hour significantly reduced finding TA by temporal artery biopsy.14 These criteria distinguish TA from other forms of vasculitis described in Table 128 –38 with 93.5% sensitivity and 91.2% specificity.14,39 Jaw claudication alone or with either scalp tenderness or a new headache increased the chances of a positive temporal artery biopsy to ⬎75%.19 Early biopsy reveals patchy segmental inflammation with infiltrated macrophages and lymphocytes limited to the elastic lamina or adventitia. This may progress to necrosis of the arterial wall with granulomas containing multinucleated histiocytes, some of foreign body type and some of Langhans’ type giant cells. Throm- 540 bosis occurs and late recanalization has been noted. Bilateral and multiple sections are necessary to confirm the diagnosis.1,6 Standard therapy for TA is corticosteroids (equivalent of prednisone, 1 mg/kg per day, for 1 month followed by a 5–10% taper every 2– 4 weeks until discontinued or the lowest tolerated dose). Prognosis is good if therapy is begun before visual loss. Visual loss has occasionally reversed.14 Duration of therapy is usually 2–3 years. Visual loss while on therapy is rare.5 In a retrospective study, aspirin appears to reduce the risk of cranial ischemic complications.39 Alternateday steroid therapy had a higher failure rate (70%) when compared with once-daily therapy (20%).40 Aziothioprine, dapsone, cyclophosphamide, infliximab, and methotrexate have not established efficacy.40 – 42 There is a case report of the successful treatment with adalimumab of relapsed TA after high-dose steroids had to be tapered.43 TCA/GA appears to be a T-cell–mediated disease. The pathogenesis involves activation of the CD4⫹ T cells, release of cytokines, activation of macrophages, and production of reactive oxygen intermediates and metalloproteinases. What factor initiates this cascade of inflammatory tissue destruction remains to be determined. The presence of dendritic cells and Toll-like receptors are one avenue of research that is being investigated.44 Interleukin (IL)-10 promoter gene and myeloperoxidase (MPO) promotor gene polymorphisms (⫺592 C/A IL-10 promoter gene and ⫺463 G/A MPO promoter gene) are associated with susceptibility to GCA.45,46 Additional History The patient’s medical history was significant for hypertension, hypothyroidism, chronic anxiety, goiter, and T-12 dermatomal zoster 2 months before this illness. She took no over-the-counter medications and denied recent travel, change in medications, or home environment. Her medications included metoprolol, levothyroxine, sertraline, alprazolam, amlodipine, and aspirin. Alprazolam-induced angioedema must be included as a specific cause of drug-induced angioedema. Alprazolam has been reported to cause allergic reactions and tongue angioedema. One such report implicated the tartrazine dye used in the drug preparation. Other benzodiazezepines have caused erythema multiforme and toxic epidermal necrolysis (tetrazepam).47–51 Laboratory and Other Diagnostic Findings A head CT scan revealed small vessel white matter changes. The initial ESR was 60 mm/hour. Her he- September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm 541 Subcutaneous nonpruritic swelling without accompanying urticaria; typical symptoms include voice change, respiratory stridor, or asphyxia Typical Presentation Acquired deficiency of C1-INH (AAE) Associated with lymphoproliferative or rheumatologic disorders. Type 1 AAE: Antiidiotype antibodies against B-cell surface immunoglobulins, resulting in formation of immune complexes. These immune complexes activate C1, which causes consumption of C1-INH Type 2 AAE: Immune blockade of the C1-INH molecule active site by autoantibodies producing a nonfunctional cleaved C1-INH Type 3: A recently described HAE exclusively found in women with mutations in coagulation factor XII gene Type 2 HAE: Normal levels of dysfunctional C1-INH Hereditary angioedema (HAE) Autosomal-dominant Prevalence 1:50,000. Type 1 HAE: Low levels of active C1-INH Pathologic Entity and Pathology Table 1 The vasculitides28-38 May present after treatment with ACE inhibitor treatment Type 3: Disease triggered by estrogen therapy, oral contraceptives, and pregnancy Type 2 has presented as food allergy May present late in life after treatment with ACE inhibitor treatment Unusual Clinical Presentations Type 1: Low C4 and C1-INH levels and normal C3, CH50 and C1q serum levels Type 2: Reduced C1-INH activity, normal serum antigen level Type 3: Two different missense mutations identified at the same position in the factor XII gene with normal C1-INH levels Diagnosis Danazol (an attenuated androgen); antifibrinolytic agents ␧-aminocaproic acid or tranexamic acid; C1-INH concentrate; recombinant transgenic C1-INH; DX-88 (ecallantide, a plasma kallikrein inhibitor); or, icatibant Treatment 542 September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm Typical Presentation Microscopic polyangiitis ANCA-associated small vessel vasculitis; proliferative GN (pauciimmune); no giant cells Often has a long prodromal phase RPGN is essentially universal; alveolar hemorrhage and gastrointestinal symptoms are common ANCA-associated primary vasculitic syndromes See Wegener’s Cutaneous manifestations: granulomatosis, ChurgPalpable purpura or Strauss syndrome, and infiltrated erythema microscopic polyangiitis May involve the small vessels around the temporal artery and present with typical manifestations of giant cell arteritis Wegener’s granulomatosis ANCA-associated Triad of upper airway vasculitis; small and involvement (which is often indolent), lower medium vessel respiratory tract necrotizing vasculitis involvement, and GN; and granulomatous abnormal CXR is very inflammation; giant common; ocular, cells present; cutaneous and proliferative GN (paucimusculoskeletal immune) manifestations are common Pathologic Entity and Pathology Table 1 Continued Central diabetes insipidus, retroorbital mass, hearing loss, thyroid, prostate and breast involvement Nodular erythema, livedo racemosa, deep ulcers, digital gangrene Unusual Clinical Presentations GN and pulmonary involvement are absent in classic PAN; p-ANCA (anti-MPO positivity is present in 60%) Tissue biopsy of site with active disease Open lung or thoracoscopic biopsy often best Renal biopsy can be supportive but is generally not diagnostic ANCA positivity is most often cANCA (anti-PR3 specificity) Diagnosis High-dose corticosteroids initially with additional immunosuppressive therapy depending on severity of disease Nonsevere or limited disease: Methotrexate Severe or generalized disease: Initial treatment with corticosteroids and cyclophosphamide Once in remission, maintenance therapy with methotrexate or azathioprine Treatment Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm 543 Takayasu’s arteritis Myointimal proliferation with vessel wall thickening and luminal stenosis, or if smooth muscle cell and elastic fiber destruction predominates, aneurysm formation Churg-Strauss syndrome ANCA-associated small vessel vasculitis; giant cells and eosinophilia present; granulomatous inflammation of the respiratory tract Pathologic Entity and Pathology Table 1 Continued Most common signs and symptoms are upper extremity claudication, asymmetric blood pressures, and vascular bruits (carotid, subclavian and aortic vessels most often) Systemic symptoms are not as common; signs and symptoms of cerebrovascular insufficiency are very common Abnormal pulmonary imaging studies are common but clinical symptoms present only ⬃25% of the time; hypertension is present in 40–80% of patients and may be underestimated in patients with subclavian and innominate artery stenosis Has prodromal, eosinophilic and vasculitic phases; typically, asthma precedes other symptoms by years; eosinophilia, pulmonary infiltrates, and mononeuritis multiplex are classic; sinusitis, allergic rhinitis, abdominal symptoms, cutaneous manifestations, and cardiac disease are common; cardiac disease is a leading cause of mortality in this disease Typical Presentation Retinopathy, vitreous hemorrhage Reversible exophthalmos; skull base infiltration with granulomas Unusual Clinical Presentations Diagnosis is based on clinical findings in the setting of compatible vascular imaging abnormalities Tissue biopsy of site with active disease (i.e. lung, nerve); has low frequency of ANCA⫹ tests; when positive usually p-ANCA (anti-MPO) Diagnosis High-dose glucocorticoid therapy (1 mg/kg per day) is the standard for those patients with relapsing disease on prednisone taper or with steroid resistant disease, methotrexate or cyclophosphamide may be added Surgical interventions include bypass, PTCA, aortic root repair or replacement; overall, bypass grafting maintains better patency Disease activity is extremely difficult to assess Primary treatment is high dose glucocorticoids; in patients with severe or refractory disease, additional agents such as cyclophosphamide or azathioprine are typically used Treatment 544 September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm Age of onset ⱖ50 year; new onset localized headache; ESR ⬎50, temporal artery tenderness, jaw claudication, amaurosis fugax, polymyalgia rheumatica, anemia, mononeuritis multiplex, and constitutional symptoms are common Aortic aneurysms can be seen as early or late complications Typical Presentation Henoch-Schonlein purpura (IgA-associated vasculitis) Capillary and venule Purpura, urticaria, abdominal involvement. IgA pain, GI bleeding, containing complexes intussusception, arthritis/ arthralgias and GN are common manifestations; often self-limited; frequently recurrent (Cutaneous) Leukocytoclastic angitis Postcapillary venules are Generally purpuric lesions the vessels most that occur in crops and commonly involved are more pronounced in Characterized by gravity-dependent areas leukocytoclasis (nuclear May have striking dependent debris from invading edema neutrophils) Giant cell arteritis Large vessel vasculitis; involvement tends to be patchy and rarely affects intracranial arteries; multinucleated giant cells present in ⬃50% of biopsies Pathologic Entity and Pathology Table 1 Continued Venous thrombosis with high levels of factor VIII and homocystein Nonproductive cough, arm claudication, tumor-like mass in the breast, SIADH, tongue infarction, hearing loss, and Charles Bonnet syndrome (visual hallucinations) Unusual Clinical Presentations Diagnosis is made by skin biopsy Suspect if patient is ⬎50 years old, PMR, FUO, unexplained anemia, new headache, acute visual changes and/or elevated ESR Temporal artery biopsy If temporal artery not clinically involved may need to biopsy other arteries such as occipital or facial Diagnosis Eliminate underlying precipitant. Treatment options include NSAIDs, colchicine, pentoxyfylline, dapsone, and shortterm low-dose steroids Compression stockings for edema In absence of renal dysfunction, symptomatic treatment; need to periodically monitor for recurrence until complete resolution of symptoms High-dose glucocorticoids and low dose aspirin (81– 100 mg/day) Treatment Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm 545 Typical Presentation Unusual Clinical Presentations Diagnosis Treatment Central nervous system isolated angiitis. Including (1) granulomatous angiitis of the CNS (GACNS) (2) BACNS (3) Atypical PACNS Cerebral Granulomatous medium Decreased cognition (83%), headache (56%), seizure angiography may vessel vasculitis limited (30%), stroke (14%), and be helpful; brain to the central nervous hemorrhage (12%) are most and system common presentations leptomeningeal Langerhans and foreignElevated ESR, and CSF protein biopsy are the body type multiare common. gold standard nucleated giant cells often present Three clinical subset: GACNS—male predominant, any GACNS: Treated with cyclophosphamide and age, with long prodromal period and classic histology on corticosteroids (see treatment for biopsy Wegener’s) BACNS—more likely female, BACNS: Glucocorticoids for ⱕ6 mo acute onset of headache or with adjunctive calcium channel neurologic symptoms, classic blockers angiogram, more often monophasic and benign course Atypical PACNS: Treated initially Atypical PACNS—most common with steroids alone presentation; does not fit the diagnostic criteria for either GACNS or BACNS Polyarteritis nodosa Medium-sized vessel Weight loss, skin nodules, livedo Breast and uterine There is no High-dose glucocorticoids are the vasculitis with reticularis, hypertension, renal involvement; rare diagnostic lab test; initial mainstay segmental transmural insufficiency, abdominal pain, vasculitis of the tissue biopsy and Patients with critical organ inflammation of blood in the stool, myalgia and cystic or appendiceal arteriography involvement (renal or muscular arteries weakness, neuropathy, arteries may mimic gastrointestinal ischemia, Unlike the ANCAtesticular pain, and an acute cholecystitis or cardiomyopathy or dense associated vasculitides association with hepatitis B appendicitis neuropathy) usually are treated it does not involve infection are common; many of with an additional veins and these are part of the immunosuppressive agent such as granulomatous classification criteria for this cyclophosphamide or methotrexate inflammation does not disease If active hepatitis B or C infection is occur May involve the small vessels present, a relatively short course around the temporal artery and of steroids in conjunction with present with typical aggressive antiviral therapy is manifestations of giant cell fairly standard arteritis Pathologic Entity and Pathology Table 1 Continued 546 September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm Typical Presentation Unusual Clinical Presentations Diagnosis Treatment Kawasaki Disease (KD) Fusiform aneurysms of Clinical i.v. immune globulin therapy and Medium vessel vasculitis Mucocutaneous lymph node brachial arteries aspirin syndrome: Fever, conjunctivitis, mucositis, polymorphous rash, Incomplete KD, in edema/erythema/desquamation which adenopathy is finding most often of hands and feet, lymphadenopathy absent Complications include coronary artery aneurysms, MI, heart failure, and arrthythmias Behcet’s disease On the basis of Severity of the illness usually More common in Middle Eastern Renal and peripheral Necrotizing improves over time; life nervous system clinical findings. men, and women from the Far leukocytoclastic expectancy is normal involvement is less ICAM-1 levels obliterative East; recurrent, usually painful common appear to correlate Major serious complication is perivasculitis and mucocutaneous ulcers (oral and blindness; mucous membrane with disease venous thrombosis; urogenital) involvement is treated with topical activity affects capillaries, veins Ocular disease present in 2/3 steroids and thalidomide can be (uveitis most common) and arteries of all sizes; used in more severe cases; Vascular disease present in 1/3, immune complex colchicine and interferon ␣ can be especially venous vasculitis thromboembolic disease used CNS disease present in 10–20% Thrombophlebitis is treated with Pathergy test positive. aspirin; uveitis and CNS disease Cutaneous disease is common require systemic high dose and varies steroids and azathioprine Anti-TNF may be an alternative treatment for panuveitis and mucocutaneous disease Cogan’s syndrome Interstitial keratitis with Glucocorticoids are the mainstay of treatment; treat as early as vestibuloauditory symptoms; possible with onset of hearing loss; may be associated with early treatment improves outcome systemic vasculitis especially aortitis with aortic valve involvement Pathologic Entity and Pathology Table 1 Continued Allergy and Asthma Proceedings Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm 547 Typical Presentation Unusual Clinical Presentations Diagnosis Treatment HAE ⫽ hereditary angioedema; ANCA ⫽ antineutrophil cytoplasmic antibody; C1-INH ⫽ C1 esterase inhibitor; ACE ⫽ angiotensin-converting enzyme; GN ⫽ glomerulonephritis; PR3 ⫽ proteinase-3; GN ⫽ glomerulonephritis; CXR ⫽ chest x-ray; RPGN ⫽ rapidly progressive glomerulonephritis; MPO ⫽ myeloperoxidase; PTCA ⫽ percutaneous transluminal coronary angioplasty; ESR ⫽ erythrocyte sedimentation rate; SIADH ⫽ syndrome of inappropriate antidiuretic hormone; PMR ⫽ polymyalgia rheumatica; FUO ⫽ fever of unknown origin; GI ⫽ gastrointestinal; NSAID ⫽ nonsteroid anti-inflammatory drug; BACNS ⫽ benign angiopathy of the CNS; PACNS ⫽ primary angiitis of the CNS; MI ⫽ myocardial infarction; ICAM-1 ⫽ intercellular adhesion molecule-1; TNF ⫽ tumor necrosis factor. Secondary vasculitides Secondary cryoglobulinemic Infection related; vasculitides may involve the secondary small vessels around the cryoglobulinemic; temporal artery and present connective tissue with typical manifestations of disease related; drug hypersensitivity-related; giant cell arteritis malignancy related hypocomplementemic urticarial vasculitis; organ transplant related; and, pseudovasculitis (antiphospholipid syndrome, atrial myxoma, endocarditis, Sneddon syndrome) Pathologic Entity and Pathology Table 1 Continued Figure 1. Low-power view of hematoxylin and eosin–stained section of the right temporal artery. Extensive transmural inflammatory infiltrate is involving the medium-size artery wall. Multinucleated histiocytes (giant cells) are frequently present in the media and some extending to adventitia where areas of prominent inflammatory infiltrate are present. Foci of medial necrosis (homogenous acellular areas) can be identified. Marked intimal thickening with edema and early fibrosis are seen also. Figure 2. Medium-power view of hematoxylin and eosin-stained section of the left temporal artery. There is marked multinucleated giant cell and epithelioid histiocyte infiltrate, forming occasionally nodular aggregates (granulomata). Some of giant cells are of Langhans’ type (peripherally lined nuclei) and some others are of typical foreign body type (random location of multiple nuclei). Other inflammatory cells visible are lymphocytes, neutrophils, and eosinophils, signifying acute and chronic inflammation. Special stains were negative for acid-fast bacilli and fungal microorganisms, in the setting of appropriate controls (not shown). moglobin was 11.4 gm/dL, (with normochromic normocytic indices). The white blood cell count was 12,400 cells/mm3 with no eosinophils and a normal 548 Figure 3. High-power view of elastic-stained section of the right temporal artery. Destruction of the wall by granulomatous inflammation is present. A group of giant cells have accumulated on the medial side of intimal-medial junction, closely approaching the internal elastic lamina (dark linear stain), in the process of phagocytosis. There is a disruption of continuity and absence of internal elastic lamina in the other area that is not involved by giant cells and showing early neovascularization. Separately, a prominent giant cell of Langhans’ type can be seen. Again, a mixed acute and chronic inflammatory infiltrate is noted. differential count. Other laboratory tests were normal or negative (cerebral spinal fluid chemistry, culture, cytology, and bacterial antigen survey; TSH; free T4; C3; C4; CH50; C1q; C1-INH; serum IgE; C1q binding assay; cryoglobulins; ANA; rheumatoid factor; antimicrosomal antibodies; antithyroglobulin antibodies; and, serum protein electrophoresis). Figures 1–3 show her pathological findings in bilateral temporal artery biopsy specimens. She was treated with antibiotics, acyclovir, diphenhydramine, and methylprednisolone (40 mg i.v. b.i.d.). Bilateral temporal artery biopsy specimens showed extensive granulomatous inflammation with disruption of the wall architecture. Final Diagnosis The headache, neck, and facial pain gradually improved over the next 5 days. She was discharged on prednisone 60 mg/day. The final diagnosis was TA. CONCLUSION This patient’s age, elevated ESR, and tenderness over the temporal areas were significant clues. The biopsy specimens and response to steroid therapy were consistent with TA. September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm REFERENCES Accetta DD, Kelley JF, and Tubbs DO. An elderly black woman with a painful, “swollen” face. Ann Allergy 55:819 – 824, 1985. 2. 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J Investig Allergol Clin Immunol 17:205–206, 2007. e September–October 2008, Vol. 29, No. 5 Delivered by Ingenta to: Guest User IP: 46.148.30.133 On: Sun, 26 Jun 2016 05:17:58 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm