Henoch-Schönlein purpura (HSP), now formally called IgA vasculitis, is caused by the abnormal buildup of a specific antibody called IgA1 in the walls of small blood vessels. This triggers inflammation that damages vessels in the skin, gut, joints, and sometimes the kidneys. The condition most commonly affects children, with a median age of onset around 5 years, and boys are diagnosed slightly more often than girls (about 56% of cases). While the immune system malfunction driving HSP is well understood, the initial trigger that sets it off varies from infections to medications to genetic predisposition.
How the Immune System Causes Damage
HSP is fundamentally a problem with one branch of the immune system: IgA antibodies. Normally, IgA helps defend your body’s mucosal surfaces, like the lining of your throat and gut. In HSP, the body produces a defective form of IgA1 that is missing key sugar molecules on its surface. This galactose-deficient IgA1 behaves abnormally. The immune system recognizes it as foreign and produces autoantibodies against it, and the two bind together to form large clumps called immune complexes.
These immune complexes are too large and structurally abnormal for the liver to clear efficiently. They accumulate in the bloodstream and eventually lodge in the walls of small blood vessels throughout the body. Once deposited, they activate the body’s complement system (a cascade of proteins that amplifies immune responses) and trigger the release of inflammatory chemicals like interleukin-6 and tumor necrosis factor. This attracts waves of white blood cells to the vessel walls, causing the swelling, bleeding, and tissue damage that produce HSP’s hallmark symptoms: the purplish skin rash, abdominal pain, joint swelling, and in some cases kidney inflammation.
Infections Are the Most Common Trigger
In roughly half of pediatric HSP cases, the disease follows an infection, most often a bacterial or viral illness affecting the upper respiratory tract. Streptococcal infection (the bacteria behind strep throat) is the single most frequent infectious trigger, identified in about 19% of HSP patients in one large study. Other documented triggers include Helicobacter pylori (4.2%), Mycoplasma pneumoniae (4.1%), parainfluenza virus, respiratory syncytial virus, and, rarely, tuberculosis and toxoplasma.
The connection between infections and HSP helps explain the condition’s strong seasonal pattern. Spring sees the highest number of cases (about 31% of annual diagnoses), peaking in March, while summer has the fewest (around 19%), bottoming out in August. This tracks closely with the seasonal rhythm of respiratory infections. In Spain, nearly 70% of pediatric HSP cases occur during fall and winter. The pattern is less pronounced in adolescents, who actually show a slight summer peak for reasons that aren’t fully clear.
The infection itself doesn’t directly cause HSP. Instead, it appears to rev up the immune system in a way that increases production of the defective IgA1 antibodies, setting off the chain of events described above. This is why HSP typically appears days to weeks after the initial infection, not during it.
Other Known Triggers
Infections aren’t the only things that can kick-start HSP. The American Academy of Family Physicians notes that the condition can also be triggered by medications, vaccinations, insect bites, exposure to certain chemicals, and cold weather. These triggers are less common than infections but are well documented in medical literature.
The mix of triggers shifts significantly between children and adults. While a preceding infection is identified in about 45% of pediatric cases, only around 20% of adult-onset cases have a clear infectious trigger. Adults are more likely to develop HSP in association with certain medications, solid tumors, or other autoimmune diseases. This difference in triggers is one reason adult HSP tends to be more severe and harder to predict than the childhood form.
Genetic Susceptibility
Not every child who gets strep throat develops HSP, which points to an underlying genetic component. Research has confirmed that specific variations in HLA genes (the genes that help your immune system distinguish your own cells from invaders) significantly increase the risk of developing the disease.
The strongest genetic association is with variants of the HLA-DRB1 gene. Certain versions of this gene have been found at dramatically higher rates in HSP patients compared to healthy controls. One variant, HLA-DRB1*12, carried nearly six times the odds of developing HSP. Another, HLA-DRB1*14, carried about five times the odds and was specifically linked to kidney involvement during the disease. Variants HLA-DRB1*10 and DRB1*11 were associated with gastrointestinal symptoms. Additional risk variants have been identified in the HLA-A and HLA-B genes.
These genetic findings vary somewhat across populations. Studies in Spanish, Italian, Iranian, Turkish, and Croatian children have each identified slightly different risk alleles, suggesting that genetic susceptibility to HSP is real but population-specific. Having these gene variants doesn’t guarantee you’ll develop HSP. It means your immune system may be more prone to the abnormal IgA1 response when exposed to the right trigger.
Why Some Cases Affect the Kidneys
The same IgA1 immune complexes that damage skin and gut blood vessels can also deposit in the kidney’s filtering units, called glomeruli. Kidney involvement is the most serious potential complication of HSP, and understanding what drives it has been a major research focus.
The defective sugar structure on IgA1 molecules plays a particularly important role here. Research has shown that abnormal IgA1 glycosylation (the sugar-coating defect) is found specifically in HSP patients who develop kidney problems, not in those whose disease is limited to skin and joints. Once these malformed immune complexes reach the kidney, they activate specialized cells in the glomeruli, triggering local production of inflammatory signals and damaging the cells that filter blood. This can lead to blood or protein in the urine and, in severe cases, lasting kidney damage.
Risk factors for kidney involvement include female sex (about three times the odds compared to males) and higher levels of systemic inflammation, as measured by the ratio of neutrophils to lymphocytes in the blood. Older children and adults also face a higher risk. Certain HLA gene variants, particularly HLA-DRB1*14:01, appear nearly four times more often in HSP patients with kidney disease than in the general population, suggesting a genetic predisposition to this specific complication.
Putting It Together
HSP results from a multi-step process. First, something goes wrong with how the body produces IgA1 antibodies, leaving them structurally deficient. Second, the immune system generates antibodies against these abnormal molecules. Third, immune complexes form and overwhelm the body’s ability to clear them. Fourth, these complexes deposit in blood vessel walls and trigger inflammation. The initial spark is usually an infection, but medications, vaccines, environmental exposures, and genetic predisposition all influence who develops the disease and how severe it becomes. In children, the process is almost always self-limiting, resolving within weeks. In adults, where the triggers and immune context differ, the course is often more complicated.