Vasculitides

Chapter 20 Vasculitides



Thomas A. Brown, MD, Sonali J. Shah




Insider’s Guide to Vasculitides for the USMLE Step 1


Vasculitides on Step 1 are very straightforward if you know the most common signs and symptoms of each diagnosis. The best way to study for this section is to simply read through the information listed in First Aid (which contains everything that you need to know for boards) and then test yourself with the tables and cases in this chapter. It is advisable that you make a list for yourself of the unique features of each disease (e.g., palpable lower extremity skin rash with Schönlein-Henoch purpura, weak upper extremity pulses in Takayasu’s arteritis, unilateral headache in temporal arteritis). These features will most likely be your biggest clues in the clinical vignettes presented to you on boards. You should also be sure to know the unique laboratory features associated with specific vasculitides, such as elevation in perinuclear antineutrophil cytoplasmic antibody (p-ANCA) or cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA), elevated erythrocyte sedimentation rate (ESR), and hepatitis B seropositivity, as the USMLE loves to test students on these facts.



Basic Concepts



1 What are the vasculitides and how do they typically present clinically?


The best way to think of the vasculitides is as a group of poorly understood autoimmune disorders involving the blood vessels. They are defined by the presence of leukocytes in the vessel walls, and as inflammatory diseases, they typically present with vague constitutional signs such as fever, malaise, and arthralgias or myalgias. A biopsy of affected blood vessels can be very helpful in making a definitive diagnosis, although obtaining a segment of affected vasculature can be difficult. Although it appears that a majority of the vasculitis syndromes are caused by an immune-mediated mechanism, other possible etiologic factors include drug hypersensitivity reactions and viral infections resulting in immune complex deposition within the vasculature.



2 Along with constitutional complaints, what clinical signs and patterns of organ involvement suggest a vasculitic syndrome?


Palpable nonblanching purpura may indicate vasculitides such as hypersensitivity (leukocytoclastic) vasculitis, Schönlein-Henoch purpura, and microscopic polyangiitis (polyarteritis).


Mononeuritis multiplex, a clinical picture that arises from simultaneous disease to multiple individual nerves, typically affects sensory and motor function. In the United States, diabetes is the most common cause of this neuropathy, but in the nondiabetic person, it is very suggestive of vasculitis, particularly polyarteritis nodosa (PAN).


Pulmonary-renal involvement, such as hemoptysis and hematuria, are suggestive of a pulmonary-renal syndrome such as Wegener’s granulomatosis or Goodpasture’s syndrome.



3 How are the vasculitides classified?


The vasculitides are generally classified by the size and types of blood vessels that are typically affected in patients with each disorder.


Large vessel vasculitis:



image Takayasu’s arteritis affects the aorta and its major branches.


image Temporal arteritis, also known as giant cell arteritis, most commonly affects the branches of the external carotid artery, characteristically including the temporal artery.


Medium-sized vessel vasculitis:



image PAN affects medium-sized muscular arteries.


image Kawasaki disease actually affects large, medium-sized, and small arteries, but the most important association is that, if untreated, it can affect the coronary arteries.


Small vessel vasculitis:



image Churg-Strauss arteritis affects the arteries of the lungs and of the skin.


image Wegener’s granulomatosis affects medium-sized and small arteries, arterioles, and venules, particularly in the respiratory tract.


image Cryoglobulinemic vasculitis affects capillaries, arterioles, and venules.


image Schönlein-Henoch purpura primarily affects venules.


image Vasculitis that is due to hypersensitivity reaction, secondary to viral infection, or secondary to connective tissue disorder typically affects small vessels.



4 Cover the right column in Table 20-1 and attempt to describe the “classic presentation” for each of the listed vasculitides


Table 20-1 lists the classic presentations of the vasculitides.


Table 20-1 Classic Presentation of the Vasculitides






























Vasculitis Classic Presentation
Temporal (giant cell) arteritis Fever, unilateral headache, markedly elevated ESR
Wegener’s granulomatosis Hemoptysis, hematuria, presence of c-ANCA
Kawasaki syndrome Unexplained fever, maculopapular rash that starts on hands and feet, bilateral conjunctival injection, cervical lymphadenopathy, edema of extremities, and mucosal changes such as strawberry tongue; seen in children
Polyarteritis nodosa Hepatitis B antigenemia is common, presence of p-ANCA; arterial biopsy reveals inflammation of the tunica media
Generally affects vessels of the kidney, heart, liver, and GI system
Does not affect the pulmonary vasculature
Churg-Strauss syndrome History of asthma, sinusitis, peripheral neuropathy
Lab tests show eosinophilia
Takayasu’s arteritis (“pulseless disease”) Fever, night sweats, arthritis, myalgia, vision problems, different blood pressures in the arms
Commonly seen in Asian women younger than 40 years of age
Henoch-Schönlein purpura Abdominal pain, hematuria with red blood cell casts, maculopapular rash on lower extremities (palpable purpura)
Most commonly occurs in young children; associated with IgA nephropathy after upper respiratory infection
Thromboangiitis obliterans (Buerger’s disease) Young male smoker with distal extremity cold intolerance

c-ANCA, cytoplasmic antineutrophil cytoplasmic antibodies; ESR, erythrocyte sedimentation rate; GI, gastrointestinal; IgA, immunoglobulin A; p-ANCA, perinuclear antineutrophil cytoplasmic antibodies.




Case 20-1


A 75-year-old Caucasian woman is evaluated for a 1-week history of anorexia, fatigue, and severe headache. She denies any recent visual problems or photophobia.



1 What are the main considerations in your differential diagnosis?


Constitutional complaints such as anorexia and fatigue are suggestive of malignancy, depression, infection, and vasculitis. The headache could be caused by a migraine, meningitis, primary or metastatic cancer, subdural hematoma, or vasculitis. However, for boards, headache in an adult over 50 in the absence of fever or head trauma is temporal arteritis until proved otherwise.




Case 20-1 continued:


Physical examination is significant for right-sided scalp tenderness. Laboratory tests reveal a markedly elevated erythrocyte sedimentation rate (ESR).



2 What is the likely diagnosis?


Temporal arteritis or giant cell arteritis (GCA). Temporal arteritis occurs almost exclusively in patients older than 50. Women are more likely than men to be affected, and rates are highest in whites. Unilateral headache and scalp tenderness are classic for temporal arteritis, as is the elevated ESR. Temporal arteritis also commonly presents with jaw pain. Vision impairment or blindness may result in the most serious cases.


The name temporal arteritis is derived from the fact that the disease preferentially targets the extracranial branches of the carotid arteries, frequently affecting the superficial temporal artery. The ophthalmic, vertebral, and the carotid arteries may also be affected.



3 What does the elevated erythrocyte sedimentation rate imply?


The ESR and C-reactive protein (CRP) are the most widely used indicators of the acute-phase protein response. Although these measurements lack specificity (being elevated in vasculitides, infections such as endocarditis, and malignancies), they are useful because the acute-phase protein response may reflect the presence and intensity of an inflammatory process.


Specifically, the ESR represents the rate at which the erythrocytes fall through the plasma, which depends largely upon the plasma concentration of fibrinogen, a protein that is seen in higher concentration during an inflammatory process.



4 In temporal arteritis, what events lead to inflammation of the artery?


It is likely that T cells and macrophages enter the artery wall via the vasa vasorum. How they become activated and targeted is as yet unknown. CD4+ T cells release interferon (IFN)-γ, and macrophages release interleukins (IL-1, IL-6) and platelet-derived growth factor (PDGF). IFN-γ mediates the inflammatory response in the vessel wall, IL-6 is largely responsible for systemic signs of inflammation, and PDGF promotes proliferation of smooth muscle cells and intimal hyperplasia. This intimal hyperplasia leads to occlusion of the arterial lumen, ultimately leading to the symptoms of ischemia experienced by the patient.




Case 20-1 continued:


The patient is started on high-dose steroids, and the following day a biopsy of a 3-cm section of the right side of the temporal artery returns as negative for signs of inflammation.



5 Why might it still make sense to treat this patient?


Temporal arteritis affects the temporal artery in a segmental fashion, and this could explain a negative biopsy result even in the presence of the disease. Furthermore, in some cases, GCA may affect other extracranial branches of the carotid artery and spare the superficial temporal artery. Therefore, if the clinician has a high index of suspicion for temporal arteritis, the patient should be treated regardless of biopsy results (making biopsy of questionable clinical value).



6 What severe complication of this disorder may be avoided by initiating immunosuppressive therapy as soon as possible?


Partial or total blindness can occur suddenly and without warning. This is caused by occlusion of the ophthalmic artery, leading to ischemia of the optic nerve. Blindness may be preceded by amaurosis fugax, which is transient visual loss, often with heat or exercise. Blindness is usually permanent but can be prevented by adequate treatment with corticosteroids, making timely diagnosis and treatment of GCA crucial.


As demonstrated in this case, patients with GCA are treated with high-dose steroids to prevent blindness.



7 What other symptomatic manifestations may be expected as a result of arterial inflammation in patients with giant cell arteritis?


Decreased blood flow in the extracranial branches of the carotid arteries caused by inflammation of those vessels can lead to symptoms such as jaw claudication, especially with prolonged talking or chewing causing an increase in oxygen demand. Occasionally, respiratory symptoms such as coughing can be seen with GCA and are believed to be a result of inflammatory involvement of branches of the pulmonary artery.


In a subset of patients, the predominant symptoms of GCA may be the constitutional signs of systemic inflammation, such as fever, fatigue, and anorexia. Fatigue is often also noted in patients with more typical presentations, such as headache or scalp tenderness. This is evidence that immune activation is not necessarily limited to vascular lesions. Patients with GCA have elevated levels of circulating monocytes, which produce IL-1 and IL-6, and the latter is a potent inducer of the acute-phase response. Release of IL-6 therefore not only leads to the elevation of the ESR that is seen in these patients but also helps explain the nonspecific systemic symptoms.



8 How can response to corticosteroids be monitored?


Remember the ESR? The drop in ESR or CRP, along with the clinical response, can be used to gauge effectiveness of corticosteroid therapy.



9 What other disease is giant cell arteritis associated with?


Polymyalgia rheumatica (PMR) consists of pain for at least 4 weeks in the muscles of the neck, shoulder, and pelvic girdle. PMR is often considered to be a form of GCA that lacks the fully developed vasculitis. Like GCA, PMR responds to steroid therapy.



Step 1 Secret


Temporal arteritis is a favorite on the USMLE. Be on the lookout for symptoms of unilateral headache, jaw claudication, vision problems, and joint pain (polymyalgia rheumatica association).

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  4. Clinical Anatomy

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Apr 7, 2017 | Posted by in NURSING | Comments Off on Vasculitides

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