Henoch-Schönlein Purpura

A 19-year-old Marine with no previous medical history presented to Forward Operating Base Geronimo theater clinic in Afghanistan for evaluation of epigastric/right upper quadrant (RUQ) abdominal pain with nausea and vomiting of 1 week’s duration. He denied bowel symptoms including diarrhea and hematochezia. The patient had been deployed for 1 week and had no rash or joint complaints at that time. He denied having fevers, chills, or myalgias. He was treated with 60 mg of intramuscular ketorolac, and his daily dose of 100 mg oral doxycycline for malaria prophylaxis was withheld.

One day later, the patient presented for follow-up with persistent symptoms of RUQ pain. He was given a gastrointestinal (GI) cocktail and sent for abdominal imaging and laboratory tests. Results included trace protein on urinalysis; normal kidneys, ureters, and bladder (KUB) radiography findings (the presence of gas was noted); normal RUQ ultrasonography findings; and no acute abnormal findings on a basic metabolic panel and a complete blood cell count.

The patient’s symptoms were thought to be a result of bloating due to the gas visualized on KUB radiographs.

The patient was seen on both of the next 2 days, during which time he had an improvement in abdominal symptoms and a shift in pain from the RUQ to the left lower quadrant. The patient began tolerating oral intake of food; however, he did have persistent bloating with nausea. He was given omeprazole, simethicone, ondansetron, and acetaminophen. He still had no rash or joint complaints during this time. His abdominal pain was thought to be gastroesophageal reflux disease.

Four days after initial presentation to the theater clinic, and approximately 10 days after initial onset of symptoms, the patient was seen again in clinic for a new onset rash on the dorsa of the feet and hands that had begun 24 hours prior. Swelling of the hands and feet was noted, more predominantly in the right hand. The patient was prescribed trimethoprim-sulfamethoxazole for presumed cellulitis. The patient never took the medication.

The next day, he followed up with progression of the rash. In 48 hours, the rash had evolved into multiple palpable purpuric lesions involving his feet, ankles, and dorsa of his hands bilaterally (Figures). The soles and palms were spared, but a similar rash was present on the buttocks. The patient also had reported having arthralgia in the right elbow, in the knees bilaterally, and in several proximal interphalangeal (PIP) joints, especially in his right hand. He also had swelling of the PIP joints and bilateral wrist pain.

Given the constellation of abdominal symptoms, rash, and arthralgia, the concern was raised for small-vessel vasculitis, specifically Henoch-Schönlein purpura (HSP). The patient was started on oral prednisone, 80 mg daily, and he was evacuated to Landstuhl Regional Medical Center (LRMC) in Germany for additional evaluation.

At LRMC, his kidney function was closely monitored and the prednisone dosage was lowered to 60 mg daily. On presentation to LRMC, the patient’s rash extended halfway up his calves. He denied pain or pruritus. His GI tract symptoms had resolved; however, he reported decreased appetite. He continued to have arthralgia of the ankles and wrists bilaterally. The recommendation for a transfer stateside for a skin biopsy with immunofluorescence to assess for immunoglobulin A (IgA) deposition, a finding necessary to support an HSP diagnosis, was made at LRMC. 

The patient was evacuated to Naval Medical Center Portsmouth in Virginia; by the time of his presentation there, his dermatologic symptoms had already begun to resolve, and a biopsy was never performed.

Discussion. HSP is a self-limited, systemic, nongranulomatous, autoimmune complex, small-vessel vasculitic syndrome with multiorgan involvement that is characterized by rash, abdominal colic, joint pain, and glomerulonephritis. It was first described in 1801 by Heberden.^1,2 

The syndrome is mainly a disease of early childhood, with 90% of cases occurring between the ages of 3 and 15 years.³ It is uncommon in adults, with an prevalence of 0.1 to 1.2 per million in adults older than 20.³ Men are affected more often than are women, with a ratio between 1.2 to 1 and 1.8 to 1.⁴ A recent history of respiratory tract infection is reported in 90% of cases. Other precipitating factors reported with adult onset of HSP include medications (eg, nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, antibiotics such as vancomycin and cefuroxime), food allergies, vaccinations, and insect bites.

The classic tetrad of HSP symptoms includes palpable purpura without thrombocytopenia and coagulopathy, arthritis, abdominal pain, and renal involvement. The clinical manifestations of HSP may develop over the course of days to weeks and may vary in the order of presentation; however, renal involvement usually presents late. The purpuric skin lesions are typically located on the lower extremities but may also be seen on the hands, arms, trunk, and buttocks.

Abdominal pain (colicky in nature, worse with food) is the most common symptom of GI tract involvement and occurs in up to 70% of cases. Other symptoms include nausea, vomiting, hematemesis, melena, and hematochezia, which are secondary to vasculitis involving the splanchnic circulation (mesenteric vasculitis). More than 30% of patients experience diffuse pain, described as “bowel angina,” typically after meals and accompanied by bloody diarrhea. Usually, skin manifestations precede GI tract manifestations. In one-fourth of cases, skin lesions occur after GI tract manifestations, as in our patient’s case.

Renal involvement is usually noted within a few days to 1 month after the onset of systemic symptoms, with most patients developing renal involvement within 3 months of skin manifestations. In adults, renal manifestations occur more commonly and tend to be more severe, including end-stage renal disease (ESRD).⁴ Urinary abnormalities are present in 25% to 50% of patients. Renal involvement is similar to IgA nephropathy, presenting with gross hematuria and mild proteinuria. Hematuria is the most common symptom and is the earliest sign of renal involvement. Persistent proteinuria and hematuria predict the development of ESRD. Renal involvement is the most important prognostic factor in determining morbidity and mortality from HSP. Most cases of HSP nephritis resolve spontaneously; only 5% progress to chronic ESRD at 5 years.

Joint involvement is seen in up to two-thirds of HSP cases. Typically, nonmigratory, nondestructive polyarthralgias occur, which are symmetric in distribution and mostly involve the knees and ankles. Joint involvement is more common in adults than in children.

Differential diagnosis. Purpura may result from hypercoagulable and hypocoagulable states, vascular dysfunction, and extravascular causes. Leukocytoclastic vasculitis (LCV) is a small-vessel vasculitis that presents with palpable purpura, most often on the lower extremities. The most common triggers of LCV are infection or exposure to a new medication. However, in many cases, a cause cannot be identified.⁵ Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.

In general, HSP and cutaneous leukocytoclastic angiitis (also called leukocytoclastic or hypersensitivity vasculitis) affect the superficial vessels of the skin. In contrast, polyarteritis nodosa, nodular vasculitis, and giant cell arteritis affect deep muscular vessels found at the dermal-subcutis interface and within the subcutis. Disseminated intravascular coagulation (DIC) results from unregulated intravascular clotting, resulting in depletion of clotting factors and bleeding. The presence of petechial or purpuric lesions in a patient with meningitis should raise concern for sepsis and DIC as a cause. A positive antineutrophil cytoplasmic antibody (ANCA) test result would be associated with Churg-Strauss syndrome, Wegener granulomatosis, and microscopic polyarteritis as causes for vasculitides. In vasculitis caused by systemic lupus erythematosus (SLE) and Sjögren syndrome, if antinuclear antibody (ANA) test results are negative, positive SS-A/Ro autoantibody results can help differentiate these conditions.

Diagnosis. The diagnosis of HSP is based on clinical signs and symptoms. Laboratory studies generally show mild leukocytosis, a normal platelet count, and occasionally eosinophilia. Levels of serum complement components are normal. IgA levels are elevated in approximately half of cases.

The diagnosis of HSP can be confirmed with a direct immunofluorescence examination of a lesional skin biopsy showing IgA-predominant microvascular immune deposits. The following laboratory tests can be useful in the evaluation of a patient with suspected vasculitis: a complete blood cell count with platelet count; an erythrocyte sedimentation rate (systemic vasculitides tend to have sedimentation rates > 50 mm/h); ANA (a positive test result suggests the presence of an underlying connective tissue disorder); ANCA (can help diagnose Wegener granulomatosis, microscopic polyarteritis, drug-induced vasculitis, and Churg-Strauss syndrome); complement (low serum complement levels may be present in mixed cryoglobulinemia, urticarial vasculitis and SLE); and urinalysis (helps detect renal involvement).

A cryoglobulin test, an HIV test, hepatitis B virus and hepatitis C virus serology, occult stool samples, an antistreptolysin O titer, and streptococcal throat culture can be considered when clinically indicated.⁶

Treatment. No specific treatment exists for HSP. Most cases are mild and need only supportive measures. Although there is evidence suggesting that corticosteroids enhance the rate of resolution of the arthritis and abdominal pain, they do not seem to prevent recurrence of disease. Aggressive therapy with corticosteroids or cyclophosphamide has not been proven beneficial in reversing renal disease except among patients with crescentic nephritis.⁷ However, some experts recommend a 6-month course of corticosteroids for patients with nephrotic syndrome and those with a reduced glomerular filtration rate. Kidney transplant can be performed in patients who progress to ESRD.

Recurrence of HSP is common, occurring in up to one-third of patients, and is more likely in patients with renal involvement. Among adults, the reported rates of ESRD range from 10% to 30% at 15 years.⁸

References:

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