Cutaneous Leukocytoclastic Vasculitis in Jose R . Reyes Memorial Medical Center : A 12 year Retrospective Study

Introduction: Leukocytoclastic vasculitis (LCV) is the commonest vasculitis of skin affecting small vessels. Objectives: To study epidemiology, etiology, clinical and laboratory features and treatment outcomes in LCV patients. Material and methods: This is a Hospital based retrospective analytical study where cases with histological evidence of LCV were collected from pathology database since January 2000 to December 2011. Records were analyzed for variables, clinical features, etiological factors, laboratory results, and treatment outcome. Results: Of total 98 cases, 70 (71.43%) were Female and 28(28.57%) Male. Mean age was 28.35 years (range 1 to 71 years). Palpable purpura was commonest presentation (74.49%) involving mostly lower limbs (91.84%). Commonest symptom was abdominal pain (27.55%), followed by arthralgia (25.51%) and pruritus (24.49%). Majority of cases had unknown etiology (69.07%). Those with documented etiology included infection (25.51%) and drugs (5.10%). Leukocytosis was commonest laboratory abnormality. Forty one percentage of patients had complete remission, 33% improved, 2 % deteriorated and 24% were lost to follow up. Conclusion: Females were more affected. Palpable purpura in lower limb was commonest presentation. Majority were idiopathic LCV. Amoxicillin and UTI were commonest among causes of drugs and infection, respectively. Commonest abnormality was leukocytosis. The majority of the cases improved with therapy.


Introduction
2][3] Vasculi s has been classifi ed based on vessel size (large, medium and small-sized vessels), severity of disease (cutaneous or systemic), clinical signs and symptoms in conjunc on with histopathologic features (American College of Rheumatology criteria), histopathologic features only (Chapel Hill Consensus Conference), and primary (idiopathic) versus secondary disease. 2 Leukocytoclas c vasculi s (LCV) is a reac on pa ern of small dermal vessels, almost exclusively postcapillary venules, characterized by a combina on of vascular damage and an infi ltrate composed largely of neutrophils, as well as fragmenta on of nuclei (karyorrhexis or leukocytoclasis).The pathophysiology of vascular injury may involve (a) the deposi on of immune complexes, (b) direct binding of an bodies to an gens in vessel walls, and (c) ac va on of leukocytes by an bodies with specifi city for leukocyte an gens (ANCAs). 4posi on is facilitated when the vessels are dilated and fl ow velocity is reduced.This explains the predilec on of LCV for the dependent parts of the body (e.g. the lower leg). 5 IgA is primarily involved, there is o en systemic involvement and the illness is referred to as Henoch-Schönlein purpura (HSP), which mainly aff ects children.Renal involvement is one of the main causes of morbidity in HSP. 5 Hypersensi vity vasculi s (HV) describes pa ents with small vessel vasculi s resul ng from drug exposure. 1Erythema elevatum diu num (EED) is a chronic, recurrent cutaneous vasculi s that usually occurs in connec on with autoimmune illnesses, infec ons (e.g.,HIV), or hematological diseases.The reason for the chronicity of the lesions, which o en last for 10 to 30 years, has not been explained precisely and its pathogenesis is also unknown. 5In ur carial vasculi s, the dura on of lesions is longer than 24 hours, there is presence of purpura and post infl ammatory pigmenta on, and symptoms of burning rather than itching as in ur caria. 1 LCV most o en manifests clinically as dependent palpable purpura distributed symmetrically.They may occur anywhere, but are most commonly found on dependent areas such as the lower legs. 2,6It is associated with the following condi ons: idiopathic (45%-55%), infec on (15%-20%), infl ammatory disease (15%-20%), drug intake (10%-15%), and malignancy (<5%). 2 The fi rst line of therapy for LCV is to eliminate elici ng infec ous agents, drugs or food or treat the underlying diseases.Medica ons include an histamines, cor costeroids, colchicines, dapsone and pentoxifylline. 4 date, there is no study inves ga ng cutaneous vasculi s at length in our ins tu on.Therefore, a retrospec ve study was conducted to determine the demographics, incidence, clinical features, possible underlying e ologies, laboratory abnormali es, management and outcomes of histologically diagnosed cases of LCV at the department of Dermatology, Jose R. Reyes Memorial Medical Center (JRRMMC).

Objectives General Objective
This study aims to determine the incidence and clinical profi les of pa ents diagnosed with LCV in a 12 year retrospec ve review at the department of Dermatology of JRRMMC from January 2000 to December 2012.

Specifi c Objectives
1. To determine the demographic profi les of pa ents histologically diagnosed with LCV. 2. To determine the incidence, common clinical features, possible underlying e ologies and common laboratory abnormali es of pa ents with LCV .3. To determine the management and outcome of these pa ents.

Material and methods
All histopathologically diagnosed cases of LCV from January 2000 to December 2012 in department of Dermatology, JRRMMC were included.All pa ents with incomplete or missing charts and those without histologic confi rma on were excluded.
Records or charts of all pa ents histologically diagnosed with LCV from January 2000 to December 2012 were retrieved and reviewed.Only the pa ents with confi rmed biopsies were included.As stated in the chart, demographic profi le, medical data such as clinical diagnosis, accompanying symptoms, loca on and distribu on of lesions, dura on of disease, laboratory results if any, possible e ologies, treatments and outcomes were recorded in the data sheet.Pa ents were considered as having extracutaneous end organ involvement based on evidence from clinical assessment, biochemistry or radiology.Renal involvement was defi ned as presence of persistent glomerular hematuria and/or proteinuria.Pa ents were considered to have renal impairment if their serum crea nine level was more than the upper limit of normal.Clinical course was divided into acute (less than 3 months) and chronic (prolonged course of at least 3 months or at least two recurrent episodes) at the me of consulta on. 9Overall cumula ve incidence was also computed.The sta s cal analysis was done by calcula on of mean and standard devia on.

Results
One hundred fi y-seven cases of LCV were documented in the pathology database at the JRRMMC department of Dermatology from January 2000 to December 2011.Histopathological diagnosis of LCV was made based on the following characteris cs: fi brinoid necrosis of vessels, neutrophilic infi ltra on of vessel walls, perivascular neutrophils, leukocytoclasis, red blood cell extravasa on and fi brin thrombus. 4Only 98 charts fi t the inclusion criteria.The unavailable charts were not included in this study.

Demographic data
The mean age of pa ents histologically diagnosed with LCV was 28.35 ± 16.79 years, with ages ranging from 1 to 74 years old.Majority of the pa ents were at the second decade of life (Table 1).Seventy (71.43%) of the pa ents were females and 28 (28.57%) were males.Females were more aff ected than males in all age groups (Table 1).

Incidence
The cumula ve incidence rate in 12 years was 0.024% (98 new histologically diagnosed cases of LCV / 399,295 new cases seen at the department of Dermatology).

Clinical diagnosis and etiologies
The majority of pa ents (53/98, 54.08%) were clinically diagnosed simply as vasculi s (Table 4).Majority of the cases 67/98 (69.07%) were idiopathic.Infec on was the next most common cause 25/98 (25.51%), and UTI (15/98, 15.30%) was the most frequent infec on.Other possible e ologies of LCV in our pa ent popula on are presented in Table 5.
Based on the criteria for systemic involvement 2 abovemen oned in the Methodology sec on, systemic involvement was detected in eight pa ents (8.16%), four each in cases diagnosed with Henoch-Schönlein purpura and hypersensi vity vasculi s.Renal involvement was the most common (4/98, 4.08%).
One of the pa ents with deranged renal func on also had abnormal crea nine levels, gastrointes nal and neurological manifesta ons.

Treatment
Oral prednisone was the most commonly used fi rstline medica on (42/98, 42.86%), followed by topical steroids and colchicine (Figure 4).Fluoroquinolones were the most commonly used an bio cs (11/

Outcomes
Majority of the pa ents improved with therapy (64%), and 10% of the pa ents resolving spontaneously without any treatment.There were no deaths (Figure 5).
Four (4.08%) pa ents were admi ed.The mean hospital dura on among admi ed in the group is 6.25 ± 4.57 days, ranging from 3 to 13 days.Of the admi ed cases, 3 resolved upon discharge and one pa ent's condi on had deteriorated and had le against medical advice.This pa ent was diagnosed with acute renal failure probably secondary to intra-renal toxic injury, hepa c encephalopathy stage I, alcoholic liver disease, conges ve heart failure and was considered to have hepatorenal syndrome.
Even though treatment with oral steroids produced the highest cure rate, it also had an equivalent high failure rate.Topical steroids had the highest rate of non-improvement (Table 6).
There is no correla on between surface area involvement and outcome.All fi ve cases with a generalized presenta on had an acute course and 4 cases subsequently resolved with treatment.

Discussion
The results of our study have shown that pa ents histologically diagnosed with LCV at the JRRMMC department of Dermatology are most commonly at the 2 nd decade of life.This is contrary to other published studies in Asia such as Malaysia 7 and Singapore 8 (mean age 36 years old) and in Australia 9 (mean age 56 years old).There are confl ic ng studies regarding sex distribu on, with some repor ng male 9 (Australia), female 8 (Singapore) or equal distribu on 7 (Malaysia).Our data is in accordance with the data of Singapore 8 .9]11 As is expected, all pa ents diagnosed with hypersensi vity vasculi s (HV) (all 11 cases) and majority of HSP pa ents (23 out of 25 cases) were acute, while cases of ur carial vasculi s (2 cases) and EED (1 case) had a chronic presenta on.
The majority of the cases in our study have an unknown e ology.Common e ologies were infec ons and drugs.This is also in accordance to studies done in Singapore 8 and Australia. 9However, unlike in these countries where the most common infec on is an URTI, our most common infec on is UTI.Amoxicillin and analgesics were the most commonly associated drugs, similar to a retrospec ve study in Spain. 11mplete blood count and urinalysis were the most commonly done laboratory work-ups by the pa ents, despite the more complete panel that the dermatologists request (liver and renal profi le, chest radiograph, ESR, CRP).However, these workups seem to be enough to diagnose concomitant infec ons and may even reveal renal impairment in some of the pa ents.An -nuclear factor, ANCA, cryoglobulins were not done at our ins tu on since our pa ents cannot aff ord such inves ga ons.These workups are reportedly unhelpful in the clinical diagnosis. 10ere were neither organ malignancies nor associa on of connec ve ssue diseases found in any of the cases reviewed in this study.Other countries report the associa on of these condi ons with LCV but this may be due to more specialized centers in their ins tu ons.

Conclusion
Our retrospec ve study revealed that in JRRMMC, LCV commonly aff ects young adults (second decade of life).A female predominance was noted.Presen ng symptom and site of predilec on are in accordance with previous studies.The most common laboratory abnormality was leukocytosis, but majority had idiopathic LCV.Infec ons and drugs were common off ending agents, usually caused by UTI and amoxicillin, respec vely.Most of the pa ents were managed with steroids and colchicine.The majority of the cases improved with therapy, and some pa ents resolved spontaneously.

Figure 1 :Figure 2 :
Figure 1: Clinical presenta ons of cases histologically diagnosed with LCV

Figure 4 :
Figure 4: Medica ons given to histologically diagnosed cases of LCV

Figure 5 :
Figure 5: Outcomes of histologically diagnosed cases of LCV from January 2000 -December 2012

Table 1 :
Distribu on of age and gender in cases histologically diagnosed with LCV

Table 2 :
Distribu on of lesions in cases histologically diagnosed with LCV

Table 3 :
Accompanying symptoms seen in cases histologically diagnosed with LCV

Table 4 :
Clinical diagnoses of cases histologically diagnosed with LCV from January 2000 -December 2012

Table 5 :
Possible e ologies of cases histologically diagnosed with LCV

Table 6 :
Outcomes of histologically diagnosed cases of LCV from January 2000 -December 2012 *N/A: Not applicable