International Journal of Research in Dermatology

Kannan R et al. Int J Res Dermatol. 2018 Aug;4(3):419-423

http://www.ijord.com

Original Research Article

DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20183169

An insight into the etiopathogenesis, clinical patterns, treatment outcome and repercussions of cutaneous small-vessel vasculitis

Rajkumar Kannan*, Muthusubramanian Chandrasekar, Sridhar Venu, Jayakalyani Vijayananth

Department of Dermatology, Chengalpattu Medical College, Tamil Nadu, India

Received: 03 May 2018

Revised: 11 June 2018

Accepted: 12 June 2018

*Correspondence:

Dr. Rajkumar Kannan,

E-mail: rajderm0002@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Cutaneous small-vessel vasculitis (CSVV) is a group of disorder which is characterised by involvement of capillaries, arterioles and venules. CSVV can be idiopathic or primary, or secondary to infection, drugs or as a part and parcel of underlying systemic disease. The aim of our study is to find out the etiological factors, treatment options and their outcome in CSVV.

Methods: We analysed 75 cases of CSVV out of patients who attended Dermatology OPD, in a tertiary care-centre from April 2017 to March 2018.The study design was descriptive study. A detailed history taking, thorough clinical examination and appropriate relevant investigations including biopsy were done for all the patients fulfilling the inclusion criteria and exclusion criteria.

Results: A sample size of 75 patients (53 women and 22 men) were included in the study. Their mean age was found to be 25 years (range 18-40). The following etiological factors were made out in our study: Benign isolated (40) patients, (53%), infective etiology (14) patients, (19%), vasculitis in background of ANA/dsDNA/ANCA positivity (12) patients, (16%), drug induced (9), patients (12%). The main clinical manifestations of CSVV in our study were found to be the following viz, palpable purpura in all 75 patients (100%), fever & malaise in 30 patients, (40%), ulcers in 30 patients (40%) arthritis/arthralgia in 15 patients, (20%). After a median follow up of 6 months, complete recovery was observed in all patients, although relapses occurred in 8 patients (11%).

Conclusions: CSVV is usually associated with other vasculitis and connective tissue disorders and patients turning ANCA positive somewhere in the course of the disease is of ominous sign and hence, it becomes mandatory to keep these patients on a long term vigil.

Keywords: Cutaneous small vessel vasculitis, Anti-nuclear antibody, Leucocytoclastic vasculitis, Fibrinoid necrosis, Vasculitic ulcers, Anti-neutrophil cytoplasmic antibody positive vasculitis

INTRODUCTION

Cutaneous small vessel vasculitis also called Immune-complex small vessel vasculitis, can be an isolated phenomenon or presenting feature of a connective tissue disorder like SLE, or can present as a severe, life-threatening syndrome, including ANCA-associated vasculitis.

Cutaneous vasculitis (CV) encompasses a wide and heterogeneous group of disorders characterized by the presence of necrotizing inflammatory lesions in the cutaneous blood vessels.1-3 They may range from an isolated CV to a severe, life-threatening syndrome, including ANCA-associated vasculitis.4

Cutaneous small-vessel vasculitis (CSVV) is a single organ vasculitis producing leucocytoclastic angiitis of cutaneous vasculature.2 The presence of three of the following five criteria given by The American College of Rheumatology (ACR) is essential for the diagnosis of CSVV. (i) age greater than 16 years at disease onset, (ii) history of taking medication prior to onset, (iii) presence of palpable purpura, (iv) presence of maculopapular rash, (v) biopsy demonstrating granulocytes around an arteriole or venule.5,6

The basic challenge thrown to a dermatologist is as such, to find out, with the help of appropriate investigations, whether the patient they deal with, is prima facie a case of cutaneous small vessel vasculitis or is it the first symptom complex of a moribund illness like SLE or a concern of infectious origin like pulmonary Koch.

METHODS

A Descriptive study of CSVV of a series of 75 patients who attended Dermatology OPD in a tertiary care centre from April 2017 to March 2018 was conducted. Etiological factors, its associations, treatment outcome and prognosis were studied using an appropriate univariate analysis.

Inclusion criteria

Inclusion criteria were patients willing to give a written consent; patients of either sex of age >18 years; patients who satisfy at least three out of five American College of Rheumatology (ACR) Criteria.

Exclusion criteria

Exclusion criteria were patients with purpuric lesions and leg ulcers due to causes other than vasculitis; patients not willing to give a written consent; patients who are on immuno-suppressants already, for any coexisting steroid responsive dermatoses; pregnant women.

Complete blood count, coagulation profile, liver and renal function tests, urine analysis, electrocardiogram were performed at the time of diagnosis in all patients, as part of routine work-up. An immunological work-up profile was carried out for ANA, dsDNA and ANCA. Serological markers of acute inflammation namely ESR and CRP were monitored. A complete Tuberculosis work-up, consisting of Mantoux, Chest radiograph, Gene-Xpert was done. The diagnosis of CSVV was based on (i) skin biopsy showing characteristic histological findings of vasculitis (neutrophilic infiltration, leucocytoclasia, fibrinoid necrosis or erythrocyte extravasation into the vessel wall) and/or (ii) the presence of typical non-thrombocytopenic palpable purpura.

Figure 1: Algorithm for work up of a patient of CSVV in the background of ANA positivity.
Figure 1: Algorithm for work up of a patient of CSVV in the background of ANA positivity.

Patients were treated with any one of the following drugs Viz., systemic steroids, colchicine, dapsone, azathioprine and methotrexate as per the clinical condition and disease severity. They were regularly followed up once in two weeks till complete recovery. ANA and ANCA, screening and titre were done once in 3 months to assess the disease severity in recalcitrant patients.

RESULTS

In our study of 75 patients, 53 were women and 22 were men, with the mean age of 25 years and the range being 18-40. The main etiological factors for CSVV in our study were the following: benign isolated (40) patients, (53%), infectious etiology (14) patients, (19%), Vasculitis in background of ANA/dsDNA/ANCA positivity (12) patients, (16%), drug induced (9) patients, (12%).

The main clinical manifestations of CSVV in our study were found to be the following viz, palpable purpura in all 75 patients (100%), fever & malaise in 30 patients, (40%), ulcers in 30 patients (40%) arthritis/arthralgia in 15 patients, (20%).

60 Patients (80%) responded to systemic corticosteroids, 11patients (15%) to colchicine/dapsone and 4 patients (5%) were treated with azathioprine/methotrexate.

They were regularly followed up once in two weeks till complete recovery, although relapses occurred in 8 patients (11%).

Figure 2: Sex distribution of cases with cutaneous small vessel vasculitis. | Men Women Total (n)=75 Women-53 Men-22
Figure 2: Sex distribution of cases with cutaneous small vessel vasculitis.
Figure 3: Etiological factors of CSVV. | 40 14 12 9 0 10 20 30 40 50 60 70 Benign Isolated Infections Collagen Vascular Disease Drugs Etiological Agents No.of Patients Distribution of Patients with Various Etiological Factors 1 9
Figure 3: Etiological factors of CSVV.
Figure 4: Cutaneous manifestation of CSVV. | 30 12 12 14 7 Only Purpura Nodules/Plaque Vesicles/Bullae Ulcer Livedo Reticularis
Figure 4: Cutaneous manifestation of CSVV.
Figure 5: Non-thrombocytopenic palpable purpura.
Figure 5: Non-thrombocytopenic palpable purpura.
Figure 6: HFMD associated cutaneous small vessel vasculitis.
Figure 6: HFMD associated cutaneous small vessel vasculitis.
Figure 7: Papular and nodular vasculitic lesion.
Figure 7: Papular and nodular vasculitic lesion.
Figure 8: M. leprae causing vasculitic ulcer.
Figure 8: M. leprae causing vasculitic ulcer.
Figure 9: A large Hemorrhagic blister in vasculitis.
Figure 9: A large Hemorrhagic blister in vasculitis.
Figure 10: Vasculitic ulcer with central eschar and perilesional erythema
Figure 10: Vasculitic ulcer with central eschar and perilesional erythema
Figure 11: HPE showing leucocytoclastic vasculitis, with angiocentric segmental inflammation.
Figure 11: HPE showing leucocytoclastic vasculitis, with angiocentric segmental inflammation.

DISCUSSION

In our study out of the sample size of 75 patients, 40 patients (53%) were found to be of the benign isolated type, which correlates very well with the previous studies wherein, benign idiopathic type accounts for 50%.

Vasculitis resulting out of infections in our study were found to be due to viral and bacterial origin Viz., Coxackie virus, M. leprae constituting 19% which correlates with the previously documented studies wherein, infections can lead on to vasculitis to an extent of 20%.19

Vasculitis occurring as part and parcel of connective tissue disorders in our study amounts to 16% which is on par with the previously established study findings of 15-20% of inflammatory etiology.19

9% of our study population were found to have vasculitis of drug induced origin which correlates with the previous established studies of 10-15%.19

After starting the patient on treatment, monitoring of disease activity and response to treatment can be assessed by the following clinical and lab parameters.

Clinical

  • 1. Existing lesions of vasculitis starts healing which is made out clinically by fading out of maculo-papular dusky red erythematous lesion leaving a hemosiderin induced post-inflammatory hyperpigmentation.
  • 2. No new lesions of vasculitis should be encountered.

Lab parameters

  • 1. Fall in the titre of markers of acute inflammation like ESR & CRP.
  • 2. Fall in the titre of ANA, dsDNA and ANCA.
  • 3. Reduction in the Brimingham Vasculitis Activity Score (BVAS)

Patients have to be monitored with repeated blood tests, once in 3 months to watch for markers of further progression of disease in the form of appearance of neoantigens and antibody like dsDNA becoming positive later in the course of the disease.20,21

In our study, in majority of patients (53%), the etiology was idiopathic. Vasculitis in the background of SLE contributed to 12 patients (16%). ANA titre and other antibodies were monitored more diligently in those patients.

In our study, one patient who was recalcitrant to treatment, progressed to ANCA positivity during the course of illness and developed endophthalmitis and interstitial lung disease.

CONCLUSION

On long term, CSVV either settles down and disappears completely or either evolves into one of the well documented vasculitis of the medium sized and large vessels supplying vital organs and thereby leads to conditions like panophthalmitis, endophthalmitis and interstitial lung disease and thus turns fatal. This happens wherein a patient of idiopathic CSVV while on treatment, at one point of time suddenly turns into ANCA positive. CSVV in the background of ANA positivity has to be investigated over a period of time for ruling out evolution of SLE, and these patients should be offered a kind of guarded prognosis for the fear of developing full blown SLE, wherein CSVV has presented, as the fore-runner of SLE.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the institutional ethics committee

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