A 50-year-old woman presents with a crop of lesions that recently appeared on her buttocks and legs. On examination, the red macules and papules range in size from a few millimeters to a few centimeters; when pressed, the lesions do not blanch or partially blanch. The patient reports joint pain over her ankles and knees, along with malaise. When questioned, she acknowledges having had a “cold” a few weeks earlier, for which her primary care provider prescribed an antibiotic. Direct immunofluorescence of the lesions reveals immunoglobulin A (IgA) deposits around the small vessels in the papillary dermis.
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Small vessel vasculitis is an immune-mediated process involving inflammation of the postcapillary venules. In this case, the patient has IgA-mediated small vessel vasculitis (Henoch– Schönlein purpura), a type of small vessel vasculitis that can involve the gastrointestinal tract, kidneys, and joints, with prognostic implications.1 When patients present clinically with small vessel vasculitis, the clinician must consider whether or not the process might have systemic as well as cutaneous involvement.
The incidence of small vessel vasculitis in adults older than 15 years of age has been reported to be 4.5 per 100,000 personyears.2 Nearly half of cases (45%) are considered to be cutaneous small vessel vasculitis (not otherwise specified), 30% are IgA vasculitis, and the remainder are other types of small vessel vasculitides (urticarial, cryoglobulinemic, antineutrophil cytoplasmic antibody-associated). Although small vessel vasculitis seems to affect all ages and genders, IgA vasculitis is more common in children, with an incidence of 20.4 per 100,000 person-years.3
Small vessel vasculitis occurs when antibody complexes lodge in the small vessels (postcapillary venules) of the papillary dermis and activate the complement system, leading to inflammation, vessel destruction, red blood cell extravasation, and clinical disease.
The antibody complexes may form in response to multiple antigens; the 4 most common are infectious agents (10%-15%), medications (10%-15%), factors associated with autoimmune connective tissue disease (15%-20%), and factors associated with neoplasia (5%).4 Triggers include viral upper respiratory infections (URIs), hepatitis C virus infection, streptococcal pharyngitis, antibiotics, rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, and solid or hematologic neoplasia.4
However, the majority of cases are idiopathic (45% to 55%). In these cases, the antibody complexes form in response to an unidentified antigen. The antibody complexes may be limited to the skin but also may involve other organs, which is why a thorough review of systems is warranted. In IgA vasculitis, the antibody complexes are composed predominantly of IgA immunoglobulins.4
Patients develop symptoms approximately 7 to 10 days after antigen exposure, although there can be wide variability in timing. The key cutaneous finding of small vessel vasculitis is palpable purpura. Typically, lesions are 3 to 6 mm in size, but they may coalesce to form larger-appearing lesions. Early lesions may partially blanch but evolve to be nonblanching or truly purpuric. Lesions may develop necrotic centers, become bullae, and ulcerate. Petechial or urticarial lesions may be present as well. Lesions tend to be located on the dependent areas of the body (typically the lower extremities) and may range in number from 10 to several hundred.1,5
In addition to these cutaneous manifestations, patients may have systemic involvement, depending on the underlying etiology. In addition to palpable purpura, adults with IgA vasculitis often have arthritis (61%), gastrointestinal symptoms including bleeding (48%), and renal insufficiency with hematuria and proteinuria (32%).5 Adults with IgA vasculitis have a higher risk of progressing to significant kidney involvement and end-stage renal disease.1,5
When a clinician suspects small vessel vasculitis, it is imperative that they perform a full review of systems and physical examination to search for evidence of systemic involvement and try to undercover an underlying cause. At the very least, laboratory tests including complete blood count with differential, complete metabolic panel, and urinalysis should be performed for patients with suspected small vessel vasculitis.
Diagnosis should be based on the results of the history, review of systems, and physical examination. If symptoms are persistent, unexplained, and there is evidence of systemic involvement, additional considerations (for adults) include testing for infectious agents (hepatitis B and C virus, HIV, antistreptolysin O titers); levels of antinuclear antibody, rheumatoid factor, serum complement, and cryoglobulins; and the presence of fecal occult blood, as well as coagulation studies, serum protein/ urine protein electrophoresis, and chest radiography (if there are pulmonary symptoms).4 Patients should be up to date on age-appropriate malignancy screening.
A skin biopsy almost always is warranted in small vessel vasculitis. Preferably 2 biopsies should be taken — 1 for routine processing and 1 for direct immunofluorescence. The biopsy should be deep enough to allow the dermatopathologist to visualize the dermal vessels, with either a punch or deep shave.
On routine processing, the histopathologic hallmark is leukocytoclastic vasculitis composed of perivascular neutrophilic inflammation and nuclear dust (leukocytoclasis) around the dermal vessels, disruption of the vessel walls with fibrin deposition, and extravasated red blood cells. For routine processing, the biopsy should be taken within 24 to 48 hours of lesion appearance to have the best chance of visualizing these diagnostic findings. The biopsy for direct immunofluorescence should be taken directly from a lesion within 24 hours of appearance and placed in Michel medium or normal saline to allow the visualization of the immune complexes, which are destroyed thereafter. IgA deposits in the vessel wall are the key diagnostic feature of IgA vasculitis.4
There are many diseases that mimic small vessel vasculitis that may be included in the differential diagnosis, including arthropod bites, a maculopapular drug eruption, and many disorders that potentially present with purpuric lesions on the lower extremities, such as pigmented purpuric dermatoses; macular purpura from sun damage, age, platelet dysfunction, or medications; and scurvy, among others. A biopsy demonstrating leukocytoclastic vasculitis is key to differentiating small vessel vasculitis from these other disorders. It becomes more difficult, however, when not all the diagnostic histopathologic findings of leukocytoclastic vasculitis are present in the biopsy specimen, particularly if the biopsy was taken from a lesion that was too new or too old. The clinician must use clinicopathologic correlation to come to an overall conclusion.4,5
Most cases of small vessel vasculitis have minimal (or no) systemic involvement and are self-limited, resolving in a matter of weeks.6 Conservative measures such as rest, leg elevation, and compression stockings may be helpful. Topical steroids can be used on skin lesions to treat associated burning or itching. If a trigger (such as a medication) can be identified, then avoidance of it may be recommended. If an underlying process (such as lupus or neoplasia) is identified, then treatment of the condition may help the vasculitis.6,7 IgA vasculitis tends to have a longer and more protracted course, often marked by recurrences over several months.6 Persistent skin lesions can be treated with dapsone or colchicine.
Prednisone may be used to enhance the rate of symptom resolution if there are severe skin lesions or systemic involvement (severe renal disease in IgA vasculitis), but it is not a good long-term medication, given its side effect profile, and it does not prevent recurrent disease or renal disease in IgA vasculitis; thus, it should not be used prophylactically.6,7 Beyond these measures, other immunosuppressant drugs, including methotrexate, azathioprine, mycophenolate mofetil, or rituximab, may be used for lesion control.
The patient in this case was presumed to have vasculitis secondary to a URI (or potentially antibiotic treatment). She was treated with topical corticosteroids, which improved her lesions over the ensuing weeks. A urinalysis revealed microscopic hematuria. She was referred to the renal team, who monitored her kidney involvement, which also improved without additional intervention.
Andrew Fischer, MD, is a board-certified dermatologist at Elite Dermatology in Houston, Texas.
- Villatoro-Villar M, Crowson CS, Warrington KJ, Makol A, Ytterberg SR, Koster MJ. Clinical characteristics of biopsy-proven IgA vasculitis in children and adults: a retrospective cohort study. Mayo Clin Proc. 2019;94(9):1769-1780.
- Arora A, Wetter DA, Gonzalez-Santiago TM, Davis MD, Lohse CM. Incidence of leukocytoclastic vasculitis, 1996 to 2010: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2014;89(11):1515-1524.
- Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR. Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet. 2002;360(9341):1197-1202.
- Shinkai K, Fox LP. Cutaneous vasculitis. In: Bolognia JL, Jorizzo JL, Schaffer JV, ed. Dermatology. 3rd ed. Elsevier; 2012:385–410.
- Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schönlein purpura in adults: outcome and prognostic factors. J Am Soc Nephrol. 2002;13(5):1271-1278.
- Saulsbury FT. Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature. Medicine (Baltimore). 1999;78(6):395-409.
- Dudley J, Smith G, Llewelyn-Edwards A, Bayliss K, Pike K, Tizard J. Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schonlein purpura (HSP). Arch Dis Child. 2013;98(10):756-763.