A 20-year-old, male, active-duty soldier presents to the emergency department of a military hospital complaining of a 3-day history of a dark red, "burning" rash. The rash started at his sock line and over the course of the past 2 days has spread proximally up his thighs and to his hands. He also developed a sore throat and scratchy voice the day before presentation.^[1]

Image courtesy of Dirk M. Elston, MD.

Skin examination shows nonblanchable, 2 mm to 10 cm macules and plaques on the posterior calves, the palms, and the soles of the feet. The lesions are not tender to palpation or warm to the touch. His hands and right ankle exhibit 1+ nonpitting edema. A urinalysis shows 2+ protein and 2+ blood, with 25-50 red blood cells per high-power field on microscopy.^[2] Immunofluorescence is negative for antineutrophil cytoplasmic antibodies.^[1]

What is the most likely diagnosis?

1. Wegener granulomatosis
2. Acute bacterial endocarditis
3. Churg-Strauss syndrome
4. Henoch-Schönlein purpura
5. Impetigo

Image courtesy of Medscape.

Answer: D. Henoch-Schönlein purpura (HSP)

A characteristic HSP rash is shown. Wegener granulomatosis generally presents with a retiform, nonpalpable purpura and involvement in the upper and lower airways, as well as the kidneys. Acute bacterial endocarditis can present with similar skin signs, but most patients also present with fever, new heart murmur, and weight loss. Patients with Churg-Strauss syndrome generally first develop severe asthma and progress to involvement in the gastrointestinal tract, peripheral nerves, skin, heart, and kidneys. Impetigo, commonly caused by Staphylococcus aureus and Streptococcus, usually begins on the face, as vesicles or pustules that secondarily form honey-colored crusts.

What is the most likely systemic complication for the HSP patient in this case study?

1. Renal disease
2. Myocardial infarction
3. Central nervous system disease
4. Hepatitis
5. Pulmonary hypertension

Image courtesy of Medscape.

Answer: A. Renal disease

Acute and chronic renal dysfunction are the most significant complications of HSP,^[3] while myocardial infarction, central nervous system disease, hepatitis, and pulmonary hypertension are not typical complications of this disorder. (In this image, immunostaining reveals the characteristic presence of immunoglobulin A [IgA] in the glomerulus of a patient with HSP nephritis.)

To reduce the risk of long-term complications in patients with suspected HSP, it is important to ensure adequate hydration and monitor for renal complications.^[4] Higher white blood count and hemoglobin levels, lower C4 complement levels, and obesity are risk factors for more severe involvement. The underlying etiology may also be important in prognosis, as the development of HSP has followed triggers as diverse as upper respiratory infections, infliximab therapy for inflammatory bowel disease,^[5] and endocarditis.^[6]

Image courtesy of Wikimedia Commons | Stevenfruitsmaak.

IgA deposition within dermal vessels (shown) supports the diagnosis of HSP, being characteristic of the disease. In most forms of leukocytoclastic vasculitis, immune complexes are destroyed by the vasculitis, but in IgA-associated vasculitides, they persist and can be revealed with direct immunofluorescence techniques.^[7]

Image courtesy of Dirk M. Elston, MD.

Histologically, leukocytoclastic vasculitis is characterized by a neutrophilic infiltrate that expands the vessel walls, typically with fibrin deposition.^[8] Nuclear fragmentation (karyorrhexis) is present and helps to distinguish vasculitis from other neutrophilic disorders, such as urticaria and the eruption of juvenile rheumatoid arthritis. The vasculitis in HSP involves only the postcapillary venules and perforating vessels, sparing deep arterioles. The absence of endothelial necrosis helps to separate it from antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides.

Image courtesy of Dirk M. Elston, MD.

In leukocytoclastic vasculitis, neutrophils accumulate around the vessels and may also appear in the overlying dermal papillae. The accumulation of neutrophils within the dermal papillae can be misinterpreted as evidence of immunobullous disease, but the presence of underlying vasculitis should point to the correct diagnosis.

Image courtesy of Dirk M. Elston, MD.

In HSP, the endothelium of the postcapillary venule is intact, but the vessel wall is expanded, containing fibrin, neutrophils, and karyorrhectic debris (nuclear fragments). Red cell extravasation is typically present and corresponds to clinically apparent purpura. The differential diagnosis of leukocytoclastic vasculitis that involves the postcapillary venule only, with no necrosis of endothelium, includes mixed cryoglobulinemia, drug-induced vasculitis, vasculitis associated with an underlying malignancy or connective tissue disease, and serum sickness.

Image courtesy of Dirk M. Elston, MD.

The arrow indicates an intact endothelial cell. The surrounding deep pink material represents fibrin. The term "fibrinoid necrosis" should be applied only when the endothelial cells are necrotic.

Image courtesy of Dirk M. Elston, MD.

Cockade purpura commonly represents postcapillary venule vasculitis. This pattern is common in acute hemorrhagic edema of childhood, a condition that may mimic HSP but runs a benign course. The disease often develops after a simple acute infection.

Image courtesy of Dirk M. Elston, MD.

The rash in acute hemorrhagic edema of childhood may present with large, round, red to purpuric lesions involving the cheeks, ears, and extremities. Tender edema of the distal extremities, ears, and face is characteristic. Systemic involvement is rare, and patients typically recover spontaneously without sequelae.

Image courtesy of Dirk M. Elston, MD.

Retiform purpura is characterized by stellate infarcts that merge into a netlike pattern. It may be caused by thrombosis, embolism, or large vessel vasculitis. The endothelium is typically necrotic, in contrast to that in HSP.

Image courtesy of Dirk M. Elston, MD.

Vasculitis disorders associated with this pattern of purpura include Churg-Strauss syndrome, Wegener granulomatosis, microscopic polyangiitis, rheumatoid vasculitis, and septic vasculitis. HSP never produces this pattern.

Image courtesy of Dirk M. Elston, MD.

Retiform purpura and digital necrosis (shown) again suggest the presence of large vessel vasculitis. In such cases, ANCA testing should be performed.

Image courtesy of Dirk M. Elston, MD.

Retiform purpura secondary to acute bacterial endocarditis (Janeway lesion) is a manifestation of septic vasculitis. Septic vasculitis typically involves a mix of vessel sizes, and thrombi are often prominent within vessels.

Image courtesy of Dirk M. Elston, MD, and Rick Keller, MD.

Coumadin necrosis is a thrombotic disorder that can result in extensive infarction. A stellate border and retiform pattern may be noted at the periphery. The condition typically presents at the beginning of Coumadin therapy, as vitamin K–dependent anticoagulants fall. The stellate pattern of central necrosis and biopsy findings of thrombosis differentiate Coumadin necrosis from HSP.

Image courtesy of Dirk M. Elston, MD.

Most patients with HSP will recover spontaneously within a few weeks and require no treatment. However, once the diagnosis is confirmed by biopsy, the patient should be monitored for renal and abdominal complications that may warrant treatment. Although oral corticosteroids are often used to treat patients with HSP, there is little data from randomized, controlled trials to indicate that these agents will effectively treat related nephritis, nor have they been found to have any effect on long-term relapse or sequelae.^[9] Rather than treating HSP with corticosteroids alone, data suggest that immunosuppressive agents, such as mycophenolate mofetil, may be effective in maintaining remission.^[10]

HSP rash of the lower extremities is again demonstrated in this image.

Image courtesy of Medscape.