Henoch-Schönlein Purpura in Northern Spain

The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed byMichel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%). In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement. (Medicine 2014;93: 106–113) Abbreviations: ACR = American College of Rheumatology, ANA = antinuclear antibodies, ANCAs = antineutrophil cytoplasmic From Divisions of Rheumatology (VC-R, JL, CM, FO-S, JR-G, EP, MAG-G, RB), Nephrology (LM, MA), Pediatrics (LA, DG-L), Pathology (MCG-V), and Dermatology (HF-L, MAG-L, SA), Hospital Universitario Marqués de Valdecilla, IDIVAL, Santander, Spain. *Drs. González-Gay and Blanco share senior authorship. Financial support and conflicts of interest: This study was supported by a grant from “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain). This work was also partially supported by RETICS Programs, RD08/ 0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). The authors have no conflicts of interest to disclose. Correspondence: Miguel A. González-Gay or Ricardo Blanco, Rheumatology Division, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla s/n., ES-39008, Santander, Spain (e‐mail: [email protected] or [email protected]). Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0025-7974 DOI: 10.1097/MD.0000000000000019 106 www.md-journal.com Copyright © 2014 Lippincott Williams & Wilkins. Unau antibodies, ESR = erythrocyte sedimentation rate, HIV = human immunodeficiency virus, HSP = Henoch-Schönlein purpura, IQR = interquartile range, RF = rheumatoid factor, SD = standard deviation, URTI = upper respiratory tract infection. INTRODUCTION The systemic vasculitides are a complex group of conditions characterized by inflammatory involvement of vessels leading to different but often overlapping manifestations. HenochSchönlein purpura (HSP) is a systemic vasculitis clinically characterized by the classic clinical triad consisting of palpable purpura, joint symptoms, and abdominal pain. However, renal involvement is the most serious complication of this vasculitis. The etiology remains unknown, but precipitating events, such as upper respiratory tract infections (URTIs) and/or drug intake, have been associated with the development of HSP. The pathogenesis of HSP also remains unknown, although several authors have confirmed the potential implication of an aberrant glycosylation of the hinge region of IgA1. Histologically, HSP is characterized by infiltration of the small blood vessels by polymorphonuclear leukocytes and the presence of leukocytoclasia. Immunofluorescence staining of tissues may reveal the presence of IgA-dominant immune deposits in the walls of the small vessels (that is, capillaries, venules, arterioles, or in the renal glomeruli).3,15,19,20,25,26,48 HSP is typically a childhood disease. While in children it is often a self-limited and benign disease, HSP in adults has been described as associated with worse clinical features and poor outcome. The severity of clinical features and outcomes vary greatly. There are a number of potential explanations for these disparate results. First, the criteria used to define HSP often vary from one series to another. Second, skin biopsy was considered an inclusion criterion in some studies; however, in clinical practice biopsy is often avoided for cases with mild vasculitic syndrome, usually younger patients. Third, patients in many studies were selected patients seen in referral centers, or even seen in nephrology referral services due to renal complications, and therefore the clinical spectrum of the disease in some series was more severe than in others. Considering these limitations of previous studies, our aim was to establish the actual clinical spectrum and outcome of HSP in all age groups, using for this purpose an unselected and wide series of consecutive patients with HSP diagnosed at a single center. PATIENTS AND METHODS We reviewed the clinical records of all patientswith a diagnosis of cutaneous vasculitis seen in our center (Hospital Universitario Medicine • Volume 93, Number 2, March 2014 thorized reproduction of this article is prohibited. TABLE 1. Criteria for Differentiating Henoch-Schönlein Purpura From Hypersensitivity Vasculitis (Traditional Format) Criterion Definition 1. Palpable purpura Slightly elevated purpuric rash over 1 or more areas of the skin not related to thrombocytopenia. 2. Bowel angina Diffuse abdominal pain worse after meals or bowel ischemia usually including bloody diarrhea. 3. Gastrointestinal bleeding Gastrointestinal bleeding, including melena, hematochezia or positive test for occult blood in the stool. 4. Hematuria Gross hematuria or microhematuria. 5. Age at onset ≤ 20 years Development of first symptoms at age 20 or less. 6. No medications Absence of any medications at onset of disease which may have been a precipitating factor. The presence of any 3 or more of the 6 criteria yields a correct classification of HSP cases of 87.1%. Data from Michel et al. 33 Medicine • Volume 93, Number 2, March 2014 Henoch-Schönlein Purpura in Northern Spain Marqués de Valdecilla, Santander, Spain) between January 1975 and December 2012. Special attention was paid to patients with a diagnosis of vasculitis seen at the rheumatology, dermatology, nephrology, pediatrics, and internal medicine divisions. In addition, we tracked information on vasculitis from the pathology division. We assessed 417 patients seen at a single center who were classified as having HSP according to the criteria proposed by Michel et al (Table 1). Patients who did not fulfill these criteria were not included in the study. These criteriawere based on the American College of Rheumatology (ACR) database andmethodology. HSP was pathologically confirmed in 110 cases by a skin biopsy showing the characteristic histologic findings consistent with leukocytoclastic vasculitis (Figure 1), including neutrophilic infiltration; leukocytoclasia; fibrinoid necrosis into the vessel wall of arterioles, capillaries, and postcapillary venules; FIGURE 1. Microscopic lower-power view of skin biopsy of a patient with Henoch-Schönlein purpura showing leukocytoclastic vasculitis. (H & E stain, original magnification × 6). (Figure courtesy of Dr. González-Vela, MD, PhD, Pathology Division.) © 2014 Lippincott Williams & Wilkins Copyright © 2014 Lippincott Williams & Wilkins. Unau and red cell extravasation. The remaining 307 patients without skin biopsy had typical nonthrombocytopenic symmetric palpable purpura (Figure 2). In addition, all of them fulfilled the criteria proposed by Michel et al. Ethical committee approval (Ethical Committee of Cantabria, Spain) was obtained to perform studies on clinical and genetic markers of patients with HSP. Clinical Definitions We used the following definitions: 1) Classification by age groups: as in previous reports, patients aged older than 20 years were considered adults and those aged ≤20 years were considered children. 2) Precipitating events: a drug or a mild infectious process (mostly an URTI) were considered as the probable precipitating event of cutaneous vasculitis if they occurred close (within the preceding week) to the onset of the skin lesions. When a patient developed cutaneous vasculitis after antibiotic or symptomatic treatment for a mild infection, both the infection and the drug were considered possible precipitating events. 3) Fever was defined as a temperature >37.7°C. 4) Joint symptoms included arthralgia with or without joint effusion (arthritis). 5) The presence of nephropathy was categorized as mild or severe. Mild nephropathy included those patients with microhematuria (≥5 red cells/high-power field) and/or proteinuria that did not reach the nephrotic range. A patient was considered to have severe nephropathy if he or she had a) nephrotic syndrome, defined as plasma albumin levels ≤25 g/L and either proteinuria of 1 g/d per m of body surface area in children, or proteinuria of >3.5 g/d in adults, with or without edema; or b) when there was an acute nephritic syndrome defined as hematuria with at least 2 of the following abnormalities: hypertension, increased plasma urea or creatinine levels, and oliguria. Renal insufficiency was considered if the plasma creatinine was >125% of the upper limit of normal. 6) Gastrointestinal manifestations included either bowel angina (diffuse abdominal pain worsening after meals) or gastrointestinal bleeding (melena, hematochezia, or positive stool guaiac test). 7) Constitutional syndrome was defined as asthenia and/or anorexia and weight loss of at least 4 kg. 8) A relapse was considered present when a patient previously diagnosed with HSP and asymptomatic for at least 1 month had a new flare of cutaneous lesions or other systemic complications (mainly renal disease) related to HSP. FIGURE 2. Typical nonthrombocytopenic palpable purpura in the lower extremities of a patient presenting with Henoch-Schönlein purpura. (Figure courtesy of Dr. López Escobar,MD, Dermatology Division.) www.md-journal.com 107 thorized reproduction of this article is prohibited. Calvo-Río et al Medicine • Volume 93, Number 2, March 2014