Abstract Immunoglobulin A associated vasculitis (IgAV), formerly called Henoch-Schönlein purpura, is a small vessel vasculitis which typically presents with upper and lower extremity palpable purpura and abdominal pain. It is the most common vasculitis in children, and is less common in adults. However, newer evidence suggests the incidence within the adult population is higher than previously reported. This case study demonstrates an adult military recruit presenting with new onset IgAV shortly after basic training. He noted a preceding upper respiratory tract infection, which is a common finding in those presenting with IgAV. The diagnosis was made by clinical findings, histopathological results and direct immunofluorescence. Adults tend to develop more necrotic and bullous lesions when compared with children. This can skew histopathology and direct immunofluorescence. There is no clear consensus in current literature for whether to obtain lesional or perilesional biopsies. Such recommendations could be particularly advantageous for adults given the abnormal lesions. This case study addresses the incidence of IgAV within the adult population, diagnostic criteria, long-term sequalea of IgAV, and the importance of a proper biopsy sight when making the diagnosis. INTRODUCTION Henoch–Schönlein purpura, also called immunoglobulin A-associated vasculitis (IgAV), is a small vessel vasculitis that is characterized by Immunoglobulin A1 complex deposition in the small vessels of joints, gastrointestinal tract, and kidneys.1 It typically presents as a non-thrombocytopenic, palpable, purpuric rash on the extremities, accompanied by abdominal pain and arthralgias.1,2 On light microscopy, IgAV is characterized by a leukocytoclastic vasculitis with a neutrophil-predominate infiltration. Under direct immunofluorescence (DIF), immunoglobulin A (IgA) deposition is found in the walls of small vessels in the mid-to-upper dermis.1 IgAV is predominantly a childhood illness, however newer evidence suggests the incidence in adults is as high as 5.1 per 100,000, 3–6 times higher than previously estimated.3 While IgAV is generally self-limited in the pediatric population, adults are at a higher risk of developing chronic renal failure.4 In both children and adults, IgAV has a strong association with upper respiratory infections, particularly streptococcus, though many viral infections are also implicated.5,6 Adults tend to develop more bullous and necrotic lesions which can skew histopathology and DIF findings, making diagnosis more difficult within an older population. IgAV is a relevant disease to the military where infections are easily spread in a young adult population, living in close quarters. Early diagnosis can be difficult without a high-clinical suspicion and a thorough understanding of the disease in adults. CASE REPORT A 19-year-old enlisted army service member presented to the emergency department with a 1-wk history of increasing epigastric abdominal pain with emesis. He had recently completed basic training, during which he was living in the barracks. He noted a bout of bronchitis several months prior to presentation. The patient reported a 2-mo history of a non-painful, non-pruritic rash on the arms and legs but sparing the face and trunk. He had also been experiencing constipation, oliguria, and dark-colored urine. Skin examination was remarkable for presence of a non-continguous, symmetric, non-blanching papular-purpuric eruption on the upper and lower extremities (Fig. 1). Laboratory investigation revealed decreased complement component 4 (C4) levels and normal blood urea nitrogen and creatinine levels. Computed tomography of the abdomen displayed mesenteric lymphadenopathy and sigmoid colon thickening. Figure 1. View largeDownload slide Non-blanching, bilateral palpable purpura on lower extremities. Figure 1. View largeDownload slide Non-blanching, bilateral palpable purpura on lower extremities. The day after admission, the dermatology service performed three separate 3 mm punch biopsies on the right lateral arm (Fig. 2). The first two biopsies were sampled from a cluster of fresh (< 18 h) purpuric lesions, and the third biopsy was taken from perilesional skin one centimeter from the nearest lesion. Hematoxylin and eosin examination showed small vessel leukocytoclastic vasculitis. The lesional sample was submitted for direct immunofluorescence study, but did not reveal antibody deposition in any diagnostic pattern (Fig. 3). DIF of the perilesional sample demonstrated IgA, and to a lesser extent immunoglobulin M and complement component 3 (C3), in superficial dermal vessels (Fig. 4). Figure 2. View largeDownload slide Non-blanching palpable purpura on upper extremity. Both lesional and perilesional biopsies were obtained. Figure 2. View largeDownload slide Non-blanching palpable purpura on upper extremity. Both lesional and perilesional biopsies were obtained. Figure 3. View largeDownload slide Direct immunofluorescence of lesional biopsy did not reveal deposition of IgA in any diagnostic pattern. Figure 3. View largeDownload slide Direct immunofluorescence of lesional biopsy did not reveal deposition of IgA in any diagnostic pattern. Figure 4. View largeDownload slide Direct immunofluorescence of perilesional biopsy demonstrating IgA deposition in the superficial dermal vessels, consistent with IgAV. Figure 4. View largeDownload slide Direct immunofluorescence of perilesional biopsy demonstrating IgA deposition in the superficial dermal vessels, consistent with IgAV. DISCUSSION IgAV is an immune-mediated vasculitis with deposition of immunoglobulin A1 into the walls of affected vessels. While there are a number of proposed factors, the exact etiology is unknown, and both environmental and genetic factors likely play a role.7 Cases of IgAV are seen throughout the year, however, many studies demonstrate a predilection for the winter months.6,8–10 It is not surprising, therefore, that many cases are anecdotally preceded by an upper respiratory infection. Group A beta-hemolytic streptococcus is the most implicated infection, though numerous bacterial and viral etiologies have been hypothesized and studied.6,11–13 One study, performed by Al-Sheyyab et al,11 found a 10-fold increase in the risk of IgAV in children with positive anti-streptolysin O titer when compared with matched controls. As new military recruits are living in the cramped quarters of the barracks during basic training, it is easy to imagine the transmission of these implicated infectious agents to individuals who are genetically prone to developing IgAV. IgAV is the most common vasculitis in the pediatric population.14 It was previously seen as an exceedingly rare disease in adults, however, newer evidence suggests it is more common than once believed.3,15,16 In 2014, Calvo-Rio et al15 published an article addressing the spectrum of disease from a Spanish hospital in which 25% of the patient’s presenting with Henoch–Schönlein purpura were over the age of 20. That same year, Kang et al16 found 30% of patient’s diagnosed with IgAV at a Korean hospital were over the age of 20. Also in 2014, Hočevar et al3performed a retrospective chart review of adults diagnosed with histologically proven IgAV and found the annual incidence of IgAV in adults to be 5.1 per 100,000 adults. This is 3-6 times higher than previously reported. Adults with IgAV tend to have worse outcomes than children.4,15–17 In a retrospective study from 2002, Pillebout et al4 found nearly one-third of adults diagnosed with IgAV developed renal failure as defined as Creatinine Clearance <50 mL/min per meter squared within four months of presentation. With a median follow up of 15 yr, 10% went on to develop end stage renal disease while one-third demonstrated renal insufficiency. In another retrospective study, García-Porrúa et al18 found 36% of adults with biopsy proven IgAV had some degree of renal sequela with a median follow up of 5.5 yr. This is in stark contrast to children, who have a spontaneous remission of renal disease in 94% of cases.17 Diagnosis of IgAV can be confirmed by either the American College of Rheumatology (ACR) criteria established in 1990, or the newer EULAR/PRES/PRINTO criteria established in 2005.17,19,20 The ACR criteria for IgAV are (1) palpable purpura; (2) age at onset ≤20 yr; (3) acute abdominal pain; and (4) biopsy showing granulocytes in the walls of small arterioles or venules. Fulfillment of two or more of these criteria yields a sensitivity and specificity of 87%.19 By EULAR/PRES/PRINTO criteria, IgAV is defined as the presence of purpura or petechiae (mandatory) with a lower limb predominance without thrombocytopenia or coagulopathy, plus one of the following: (1) abdominal pain; (2) histopathology with DIF positive for IgA; (3) arthritis or arthralgia; and (4) renal involvement.20 These criteria, unlike ACR’s, were studied only in a pediatric population and have a sensitivity of 100% and specificity of 87%.20 Our patient met criteria for IgAV using both diagnostic criteria. Diagnosis can be difficult in the adult population if the clinician does not have a high-clinical suspicion. Patients over the age of 20 who develop IgA-associated vasculitis tend to have a higher frequency of necrotic purpura, with one study reporting 60% of adult patients develop hemorrhagic necrotic lesions.17,21 Cutaneous necrosis is uncommon in pediatric cases, and affects fewer than 5% of patients.22 In adult IgAV cases, 16% of patients have been reported to develop bullae.23 Bullous and necrotic lesions may yield a negative DIF result on biopsy.24,25 Our patient was 19-years-old, which may have contributed to the negative DIF findings in the lesional sample, but positive DIF on the perilesional sample. Our case suggests that there may be benefit to sampling perilesional skin in the older patient population, particularly the population encountered in the active duty military population. Recently, more authors have addressed the need to define appropriate cutaneous biopsy techniques. In 2013, Sleiman et al26 published an article addressing the lack of research for proper skin biopsy technique for light microscopy; however, the article does not mention the protocol for DIF. In a 2012 study by Linskey et al,27 DIF samples from hospitalized IgAV patients were reviewed. The authors discussed the possibility that negative DIF findings could be due to sampling location.27 The authors suggest that a study comparing lesional vs. perilesional skin biopsies in IgAV patients could determine if sampling perilesional skin may be of benefit.27 Adults would be expected to benefit most from perilesional sampling, as they tend to have more atypical purpura and clinical presentation. Walter Reed National Military Medical Center has the only Direct Immunofluorescence lab in the Department of Defense. The clinician obtaining tissue samples should consider obtaining lesional and perilesional biopsies. For best results, collect a four mm punch biopsy for DIF and place in Michel’s medium for transportation to Walter Reed. An order for DIF must be placed in CHCS1 or AHLTA (two separate orders are necessary if you are also sending a biopsy for Haemotoxylin and Eosin staining). Included in the order should be patient identifiers, biopsy site, clinical history, and sample description (lesional vs. perilesional). IgAV is more common in the adult population than previously reported, and is more commonly seen in the winter months.13,15,16 It is frequently preceded by an upper respiratory tract infection.4–6 Military recruits, living in close quarters where infectious transmission is common, are a potentially vulnerable population. Lesions on adults are more commonly necrotic or bullous, leading to a higher false-negative rate on DIF, making diagnosis more difficult when compared with the pediatric population.24,25 More research into biopsy sampling location (lesional vs. perilesional) would help guide clinicians in making a diagnosis of IgAV. Adults are at an increased risk of developing long-term renal complications when compared with their pediatric counterparts.15,16 Early diagnosis and management of such complications is important for improved outcomes. This case outlines the need for high-clinical suspicion to aid in the diagnosis of IgAV in the active duty population. References 1 Sohagia AB, Gunturu SG, Tong TR, Hertan HI: Henoch-schonlein purpura – a case report and review of the literature. Gastroenterol Res Pract 2010; 2010: 597– 648. Google Scholar CrossRef Search ADS 2 Zhang Y, Huang X: Gastrointestinal involvement in Henoch-Schonlein purpura. Scand J Gastroenterol 2008; 43( 9): 1038– 43. 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Google Scholar CrossRef Search ADS PubMed 21 Tancrede-Bohin E, Ochonisky S, Vignon-Pennamen MD, Flageul B, Morel P, Rybojad M: Schonlein-Henoch purpura in adult patients. Arch Dermatol 1997; 133: 438– 42. Google Scholar CrossRef Search ADS PubMed 22 Cream JJ, Gumpel JM, Peachey RDG: Schonlein-Henoch purpura in the adult. Q J Med 1970; 39: 461– 84. Google Scholar PubMed 23 Langford CA: Vasculitis. J Allergy Colin Immunol 2010; 125: S216– 25. Google Scholar CrossRef Search ADS 24 Gonzalez LM, Krysicka Janniger C, Schwartz RA: Pediatric Henoch Schonlein purpura. Internat. J Dermatol 2009; 48( 11): 1157– 65. 25 Saulsbury ST: Hemorrhagic, bullous lesions in Henoch Schonlein purpura. Pediatr Dermatol. 1998; 15( 5): 357– 9. Google Scholar CrossRef Search ADS PubMed 26 Sleiman R, Kurban M, Abbas O: Maximizing diagnostic outcomes of skin biopsy specimens. Int J Dermatol 2013; 52: 72– 8. Google Scholar CrossRef Search ADS PubMed 27 Linskey KR, Kroshinsky D, Mihm MC, et al. : Immunoglobulin-A–associated small-vessel vasculitis: a 10-year experience at the Massachusetts General Hospital. J Am Acad Dermatol 2012; 66( 5): 813– 22. Google Scholar CrossRef Search ADS PubMed Published by Oxford University Press on behalf of Association of Military Surgeons of the United States 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Military Medicine – Oxford University Press
Published: Mar 26, 2018
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