The enigma of adult onset Henoch Schoenlein purpura and leucocytoclastic Vasculits: a case report

INTRODUCTION

Vasculitis refers to inflammation of the blood vessels leading to tissue destruction with or without organ damage. It is classified as small, medium or large vessel vasculitis and may be either idiopathic or associated with an underlying disease. Cutaneous LCV is usually confined to small-vessel involvement of skin with rare extracutaneous manifestations in less than 30% of the cases.¹ The terms cutaneous LCV, cutaneous small-vessel vasculitis and cutaneous leukocytoclastic angiitis are all used interchangeably for this type of skin-predominant vasculitis. We report an adult male who presented with the key clinical features of cutaneous leukocytoclastic angiitis and was diagnosed as Henoch Schoenlein purpura.

CASE REPORT

A 39 year old male presented with multiple itchy, reddish raised lesions over the trunk, limbs and back since one month. Lesions initially appeared over the legs, gradually progressing to involve the thighs, abdomen and upper limbs. He denied history of photosensitivity, fever, coryza, cough, constitutional or systemic symptoms and antecedent drug intake but reported occurrence of a similar episode one year ago which had resolved spontaneously. Examination showed multiple partially blanchable purpuric papules distributed bilaterally over the lower and upper limbs, trunk, abdomen and back, palms and soles. Face was conspicuously spared. Deep dermal tenderness sign was positive. Edema with tenderness were present over hands and feet. Few coalescing haemorrhagic vesicles with central necrosis and crusting were seen on the left forearm (Figures 1-4). Mucosae were unremarkable. A week later, during his stay in the dermatology ward, he developed pain and swelling in both knee joints with abdominal cramps, bloody diarrhoea and burning micturition. Based on the history and clinical findings, we kept cutaneous small vessel vasculitis due to cutaneous LCV or adult-onset Henoch Schoenlein purpura as our differential diagnosis.

Routine investigations like complete blood count, liver function tests and renal function tests were within normal limits. 24-hour urinary protein showed microalbuminuria. Stool examination showed occult blood.

His CRP was positive and ESR was elevated (47 mm/hr). RA (Rheumatoid factor), ASO (Anti Streptolysin O) titre and screening for Hepatitis B and C, HIV-ELISA and VDRL were also negative. Ultrasonography of abdomen and pelvis, Chest X-ray, Doppler of bilateral lower limbs, radiological examination of the knee joints were unremarkable. His ANA (ELISA) was positive while the ANA blot by enzyme Immuno-Assay was inconclusive.

Histopathology of the lesion showed unremarkable epidermis with moderate to focally dense perivascular collection of neutrophils, lymphocytes, macrophages and occasional eosinophilic inflammatory infiltrate with extravasation of RBCs and focal karyorrhexis which were consistent with the findings of leukocytoclastic vasculitis (Figure 5). Immunofluorescence and serum IgA levels could not be performed because of the financial constraints. A final diagnosis of adult-onset Henoch Schoenlein purpura was made based on EULAR criteria (European alliance of associations for rheumatology) criteria.

He was started on intravenous antibiotics (ceftriaxone 1 gm IV 12 hourly, metronidazole 400 mg IV 8 hourly) along with prednisolone (0.75 mg/kg/day for 5 days) which was gradually tapered to 0.5 mg/kg/day as the existing lesions flattened and started resolving, Tablet hydroxychloroquine 400 mg twice a day and vitamin C supplements (Figure 6). Supportive measures like limb elevation and rest were also given. Gradually his abdominal and joint complaints regressed with marked improvement in lesions. Currently he is under regular follow-up.

DISCUSSION

Small vessel vasculitis can be classified as primary and secondary. Primary causes include Henoch Schoenlein purpura, essential mixed cryoglobulinemia and cutaneous leukocytoclastic vasculitis while secondary causes comprise drugs, infections (Table 1).²

LCV is a small vessel vasculitis characterized histo-pathologically by immune complex-mediated vasculitis of the dermal capillaries and venules. Cardinal clinical features of cutaneous leukocytoclastic angiitis include palpable purpura, lower extremity location, small vessel involvement.^3-5 Only one-third of patients may present with trunk and upper extremity involvement as seen in our case.⁶

LCV is idiopathic in approximately 50% of the cases. Other causes include infection (15-20%), inflammatory disease (15-20%), drugs (10-15%), and malignancy (<5%).⁷ Infections and drugs are the most common triggers for secondary leukocytoclastic vasculitis.⁸ It can be seen in association with underlying systemic autoimmune diseases, chronic infections, and malignancies.

Post-infectious leukocytoclastic vasculitis is most often seen after streptococcal upper respiratory tract infection. Other infectious triggers include, but are not limited to, Mycobacterium, Staphylococcus aureus, Chlamydia and HIV. In our case, a definitive infective focus could not be identified. Although the patient experienced an episode of bloody diarrhoea with abdominal cramps, these symptoms could be attributed to a manifestation of the vasculitis itself rather than gastrointestinal infection.

Several drugs reported to be associated with leukocytoclastic vasculitis are beta-lactams, erythron-mycin, clindamycin, vancomycin, sulphonamides, furosemide, allopurinol, NSAIDs, amiodarone, gold, thiazides, phenytoin, beta-blockers, TNF-alpha inhibitors, selective serotonin reuptake inhibitors, metformin, warfarin, valproic acid, among many others. There was no contributory drug history in our case.

Neoplastic causes include, leukemias, visceral tumors such as intestinal adenocarcinoma and lung cancer, all of which were excluded.

Systemic diseases like systemic lupus erythematosus (SLE), Sjogren syndrome, inflammatory bowel disease, Behcet disease, and rheumatoid arthritis, cryo-globulinemic vasculitis, hypocomplementemic urticarial vasculitis, and erythema elevatum diutinum are also associated with leukocytoclastic vasculitis.⁹ As LCV is a well-documented non-specific cutaneous manifestation of SLE, we performed a thorough evaluation for any associated connective tissue diseases, but were unable to find any evidence other than a positive ANA, which might indicate the possibility of an unspecified connective tissue disorder.¹⁰ However, our patient did not meet the requisite criteria for SLE or any other autoimmune disorder.

One of the differentials in this case was adult onset HSP, a disease that shares many clinicopathological features with LCV. According to the EULAR 2010 criteria, a patient is said to have HSP if he/she has palpable purpura, not thrombocytopenic/petechiae (mandatory criteria) with at least or more than one of the following; diffuse abdominal pain, histopathologyis typical LCV with predominant IgA deposits or proliferative glomerulonephritis with predominant IgA deposits, arthritis or arthralgias, renal involvement (proteinuria >0.3 g/24 h or >30 mmol/mg of urine albumin to creatinine ratio on a spot morning sample; and/or hematuria, red blood cell casts >5 red cells per high power field or ≥2+ on dipstick or red blood cell casts in the urinary sediment).¹¹ Our patient had non-thrombocytopenic palpable purpura (a mandatory criteria) along with histopathological evidence of LCV, arthralgia, diffuse abdominal pain and microalbuminuria, thereby satisfying 3 out of 5 criteria. However, we could not demonstrate the pathognomonic IgA deposition on direct immunofluorescence staining due to lack of resources. HSP commonly occurs in children (90%) with only 3.4 to 14.3 cases per million reported in the adult population.¹² Important predictors of renal disease are age of onset, presence of renal impairment, hematuria and abdominal pain at `onset, persistent eruption and renal pathology with fibrinoid necrosis and number of sclerotic glomeruli.¹³

Like LCV, HSP is thought to be triggered by a broad spectrum of antigens comprising infectious agents, tumours, auto-immune connective tissue disorders, drugs.

Evaluation of patients presenting with small vessel vasculitis should include complete and differential blood count, erythrocyte sedimentation rate, urine analysis with microscopy, liver and renal function tests, infectious serologies/cultures (blood, urine, swabs), chest X-ray, ultrasonography of abdomen and pelvis, Hepatitis B, C, HIV screening, skin biopsy (haematoxylin and eosin, direct immune fluorescence) and stool examination.

Additional investigations constitute RA factor, ASO titres, antinuclear antibody/extractable nuclear antigen, complement (CH50, C3, C4), anti‐double stranded DNA (anti-ds DNA), antineutrophil cytoplasmic antibodies (proteinase‐3/myeloperoxidase), gastrointestinal eval-uation/stool guaiac test for occult blood.

Patients with idiopathic cutaneous LCV may exhibit various disease patterns as seen in our patient. Most cases self-resolve within 3-4 weeks. Some patients may flare only intermittently, perhaps for 2 weeks every other year; others have recurrent flares every 3-6 months or intractable disease with new lesions almost every day or week for years. Our patient had a history of similar episode in the past which had resolved spontaneously.

Identifying and controlling triggers or exacerbating factors such as prolonged standing, alcohol use or specific drug use can help as can wearing compression stockings and keeping the feet elevated. Bed rest can accelerate the regression of skin lesions.

Diet has long been implicated as an inciting factor for clinical cutaneous manifestations such as LCV. Two case series have shown moderate success in the treatment of cutaneous LCV with empiric elimination diets. Bland, low‐antigenic diets were shown to prevent recurrences of palpable purpura, as well as to decrease serum levels of either immune complexes or cryoglobulins.¹⁴

Colchicine (0.6-1.8 mg/day) and dapsone (anti‐inflam-matory effect) have shown clinical resolution in patients with vasculitis. Prednisolone (initial doses of 0.5–1 mg/kg daily), with prolonged tapering to prevent rebound, can be very effective to treat acute or single episode of LCV. For recurrent, chronic, symptomatic idiopathic vasculitis, steroid‐sparing agents, such as azathioprine, mycophenolate mofetil, and cyclosporine can be given.¹⁴

Most common organ involved in LCV is the skin, which mainly manifests as palpable purpura predominantly on dependent areas such as lower limbs and buttock region, however, other dermatological lesions such as maculopapular rash, urticaria, nodules and ulceration can be the presenting complaints. Our case presented with vesico-bullous and hemorrhagic necrotic skin lesions, which occur in 35% individuals.^12,15 In 50% of cases of LCV, other systems such as renal, gastrointestinal, pulmonary, cardiovascular, and central nervous may be involved. Vasculitis involving the kidneys associated with hematuria and proteinuria can be life-threatening.¹⁶

CONCLUSION

Adult-onset Henoch Schoenlein purpura, although rare and likely to be missed, deserves a place in the differential diagnosis of cutaneous small vessel vasculitis. Management of cryptogenic leukocytoclastic vasculitis can be challenging. All patients presenting with palpable purpura must undergo thorough workup to identify any underlying cause. Also, more research is warranted to establish if LCV and HSP are harbingers of connective tissue disease emphasising the need for a long-term follow-up with stringent clinical and laboratory monitoring.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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