Henoch-Schonlein purpura associated with HLA-B27 positive axial spondyloarthritis in a young man

Abstract

Axial spondyloarthropathies are characterised by bilateral sacroiliitis, asymmetric oligoarthritis, association with the human leucocyte antigen (HLA)-B27, enthesitis and dactylitis. Although IgA nephropathy has a well-documented association with seronegative spondyloarthropathies, the association with Henoch-Schonlein purpura (HSP) has been documented only in few case reports. The present case is that of a 26-year-old man who presented with fever, lower limb arthritis, abdominal pain, palpable purpura over the buttocks and lower limbs, and clinical features of sacroiliitis. His blood tests showed elevated inflammatory markers and rheumatoid factor was negative. CT scan of the sacroiliac joints confirmed sacroiliitis. Skin biopsy revealed neutrophilic small vessel vasculitis. HLA-B27 was positive in blood. A diagnosis of HSP with HLA-B27 positive axial spondyloarthritis was made. HSP can be associated with HLA-B27 positive axial spondyloarthritis and has to be considered while evaluating for causes of cutaneous small vessel vasculitis in such patients.

Background

Spondyloarthropathies are a group of disorders that include ankylosing spondylitis, non-radiologic axial spondyloarthritis and arthritis associated with psoriasis, inflammatory bowel disease, reactive arthritis and others. The defining features of this group of disorders include bilateral sacroiliitis, asymmetric oligoarthritis, enthesitis, dactylitis and association with human leucocyte antigen (HLA)-B27. Other manifestations are anterior uveitis, inflammatory bowel disease, psoriasis, cardiovascular disease, cauda-equina syndrome, IgA nephropathy and renal amyloidosis.^1–4 Here, we describe a rare presentation of a patient with HLA-B27 positive axial spondyloarthritis, who presented to us with Henoch-Schonlein purpura (HSP).

Case presentation

A 26-year-old man presented to us with low-grade intermittent fever and bilateral lower limb swelling which he had for the past 4 months. During the last 10 days of the period, he had developed diffuse non-colicky abdominal pain, inflammatory lower backache with buttock pain and rash over the buttocks and lower limbs. There was no history of melena or hematochezia. He had significant loss of weight and appetite over the 4 months mentioned. He did not have any comorbid illnesses, addictions, allergies or significant family history.

On presentation to the emergency department, he was afebrile, with a blood pressure of 100/70 mm Hg in both upper limbs. His heart rate was 78 beats/min, respiratory rate was 18 breaths/min and arterial oxygen saturation on room air was 98%. He was noted to have pitting pedal oedema of both lower limbs up to the mid-calf, crusted papules in the foot and lower third of the leg, and palpable purpura on the lower half of the leg and extensor aspect of both elbows. On examination of the abdomen, there was diffuse tenderness, but no rebound-tenderness. His knee and ankle joints were swollen, warm and tender. Modified Schober’s test, Patrick’s test and Pump-handle test were positive suggestive of restriction of movement of lumbar spine and sacroiliitis. There were no positive findings on examination of the other systems.

Differential diagnosis

The differential diagnosis of palpable purpura that were considered included vasculitis syndromes involving small cutaneous vessels such as HSP, ANCA-associated vasculitis, cryoglobulinemic vasculitis, rheumatoid vasculitis, systemic lupus erythematosus, Behcet’s disease, inflammatory bowel disease and sarcoidosis. Rarer causes that were also considered included chronic infections causing vasculitis (bacterial—leprosy (Lucio’s phenomenon), Mycobacterium tuberculosis, Staphylococcus and Streptococcus; viral—herpes simplex, cytomegalovirus; fungal-candida, histoplasmosis; parasitic-plasmodium, schistosomiasis), neoplastic causes (chronic lymphocytic leukaemia, mycosis fungoides, Hodgkin’s lymphoma, myelogenous leukaemia and solid organ malignancies involving colon, prostate and kidney), hypersensitivity vasculitis and urticarial vasculitis.

The absence of uveitis and genital ulcers made Behcet’s disease less likely. Rheumatoid arthritis is not associated with sacroiliitis. In the presence of abdominal pain, palpable purpura involving the buttocks and lower limbs and lower limb arthritis, HSP was considered the most likely clinical diagnosis. However, this did not explain the presence of sacroiliitis and therefore the patient was evaluated further.

Investigations

The patient was evaluated with a provisional diagnosis of small vessel vasculitis and axial spondyloarthropathy. His initial blood investigations showed leukocytosis (table 1). His inflammatory markers were elevated. His antibody titers were not raised. X-ray film and CT scan of the sacroiliac joints were suggestive of bilateral sacroiliitis (figure 1). HLA B-27 was positive. Biopsy of his skin revealed neutrophilic small vessel vasculitis with C3 deposits seen on direct immunofluorescence (figure 2). An oesophago-gastro-duodenoscopy showed gastric erythema and a colonoscopy showed mucosal erythema and erosions in the sigmoid colon. Biopsy from the sites showed patchy, mild, chronic active ileitis. The features were non-specific and they were not consistent with inflammatory bowel disease. A final diagnosis of co-existent HSP and HLA-B27 positive axial spondyloarthritis was made, as he satisfied both the Assessment of Spondyloarthritis International Society (ASAS) criteria for axial spondyloarthritis and the (European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society (EULAR/PRINTO/PRES) criteria for HSP.^{5 6}

Table 1.

Lab investigations

Investigations	Result (normal range)
Haemoglobin (g/L)	112 (140–175)
Total count (x109/L)	30 (4.5–11.0)
Differential count (%)	N 85, L 8, M 4, E 1
Platelet count (x109/L)	759 (150–350)
HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) serology	Negative
Serum creatinine (μmol/L)	50.3 (8–106)
Erythrocyte sedimentation rate (mm/hour)	125 (0–20)
C reactive protein (nmol/L)	1304 (<28.5)
Antinuclear antibody	Negative
Rheumatoid factor	Negative
Cytoplasmic antineutrophil cytoplasmic antibodies (U/mL)	<2 (<2)
Perinuclear antineutrophil cytoplasmic antibody (U/mL)	<2 (<2)
Thyroid stimulating hormone (μLU/mL)	1.5 (0.4–4.2)
Blood culture	No growth
24 hours urine protein (mg/day)	132 (50–150)
Human leucocyte antigen-B27	Positive

Figure 1.

X-ray film (A) and CT bone window (B) axial sections through bilateral sacroiliac joints showing symmetrical regions of sclerosis with irregular articular surface erosions and mild reduction in joint space.

Figure 2.

(A) Photomicrograph showing perivascular inflammatory cell infiltrate (H&E x200). (B) Infiltration of neutrophils around the vessel and in the vessel wall (H&E X400).

Treatment

The patient was started on non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief. He had spontaneous resolution of skin lesions and abdominal pain. However, since he also had HLA-B27 positive axial spondyloarthritis, he was started on methotrexate and sulphasalazine. He was evaluated by a physiotherapist and initiated on a supervised exercise programme prior to discharge.

Outcome and follow-up

On follow-up the patient was found to have had complete resolution of skin lesions and to be completely relieved of pain. He was continuing exercises at home and was independently performing all activities of daily living at 5 months of discharge, off NSAIDs.

Discussion

The spondyloarthropathies include ankylosing spondylitis, non-radiologic axial spondyloarthritis and arthritis associated with psoriasis, inflammatory bowel disease, reactive arthritis and others.⁷ The defining features of these disorders include bilateral sacroiliitis, asymmetric oligoarthritis, association with the human leucocyte antigen HLA-B27, enthesitis and dactylitis, although all these need not be present at the same time in an individual. The latest classification criteria by ASAS takes into account all these factors.⁵

The clinical manifestations of axial spondyloarthritis, apart from the musculoskeletal system include anterior uveitis, associated inflammatory bowel disease, psoriasis, cardiovascular disease including acute coronary syndrome, cerebrovascular accident, abnormalities of the conduction system, diseases of the aortic root and valve, and venous thromboembolism.^{1 2} Rarer associations are cauda-equina syndrome, IgA nephropathy and renal amyloidosis.^{3 4}

IgA nephropathy and HSP are considered to be related disorders, and the association with IgA nephropathy and seronegative spondyloarthritis has been well documented.^{8 9} However, there have only been few case reports of patients presenting with HSP and seronegative spondyloarthritis.^10–15

In our patient mentioned here and others cited in literature, the severity of arthritis coincided with nephropathy and cutaneous vasculitis. This suggests a common mechanism of pathogenesis. This is supported by the finding of increased levels of IgA in the serum and IgA deposits in the dermal vessels of asymptomatic patients with ankylosing spondylitis.^{16 17}

The role of the gut microbiome in the pathogenesis of spondyloarthropathies is a rapidly expanding field of research.¹⁸ IgA is the most abundant antibody secreted in the gastrointestinal mucosa.¹⁹ Hence, the pathogenesis of HSP and seronegative spondyloarthritis may represent the final event in a series of interactions between the host immune system and an altered gut microbiome. It is also interesting to note that it is the IgA1 subclass of IgA that is elevated in seronegative spondyloarthritis and not the IgA2 subclass that is secreted into mucosal surfaces.¹⁶ We hypothesise that the elevated IgA1 subclass may represent a dysfunctional immune response to gastrointestinal inflammatory trigger or a compensatory increase due to an inadequate IgA2 response, which in turn may lead to both HSP and IgA nephropathy.²⁰ Serum IgA anticardiolipin antibodies may also have a role in the pathogenesis of both diseases.^{21 22}

HSP induced by treatment of patients with ankylosing spondylitis with etanercept (a TNF alpha blocker) has been reported.²³ Serum IgA has been known to downregulate the levels of tumour necrosis factor-alpha and blockade of the latter has been shown to elevate IgA levels. This further alludes to the role of IgA in the pathogenesis of HSP.^{24 25}

At present, our understanding of these complex mechanisms of pathogenesis of these diseases remains incomplete. There is a need for further research in these fields to elucidate the precise mechanism of these diseases. This research may also reveal opportunities for the development of drugs which target specific molecules that are central to pathogenesis. Indeed, the development of biological response modifiers have multiplied our therapeutic armamentarium in recent years.

Patient’s perspective.

I am satisfied and happy with the treatment given to me. I am independent and can look after myself. However, my family is very supportive especially my brother and sister-in-law, who looked after me throughout my stay in the hospital. I am pleased with all the attention and care I received in the hospital. The doctors and nurses were nice to me.

Learning points.

• Henoch-Schonlein purpura (HSP) can be associated with human leucocyte antigen (HLA)-B27 positive axial spondyloarthritis.

• IgA has a central role in the pathogenesis of HSP in patients with HLA-B27 positive axial spondyloarthritis.