What is This Rash in an Elderly Long-Term Care Resident?

An 82-year-old man who resided in a long-term care facility developed an upper respiratory infection, which was characterized by a nonproductive cough and a low-grade fever. A chest radiograph showed no abnormalities, and the patient was treated with a fluoroquinolone. Five days after treatment initiation, the patient developed a nonpurpuric rash, which was predominantly on his thighs, forearms, and buttocks, with no involvement of his back, chest, or face (Figures). The patient also reported passing dark, coffee-colored urine, but he had no associated urinary urgency, frequency, or burning. He also had no headaches, neck stiffness, or photophobia. 

Three days after the rash had developed, serial laboratory tests indicated worsening renal function. The patient’s creatinine level increased from 1.6 mg/dL at baseline to 2.8 mg/dL (normal, 0.6-1.3 mg/dL), and his albumin-to-creatinine ratio was elevated above normal at 94 mcg/mg (normal, <30 mcg/mg). A complete blood count was normal except for a low hemoglobin level of 10.4 g/dL (normal, 13.8-17.2 g/dL), indicating mild anemia. Review of a urinalysis showed hematuria with a red blood cell (RBC) count of >180 RBC per high power field (normal, 0).

Figures. Images showing the rash on the patient’s arm and leg.

Based on the case description and photographs, what is your diagnosis?

1. Henoch-Schönlein purpura
2. Idiopathic thrombocytopenic purpura
3. Poststreptococcal glomerulonephritis
4. Fluoroquinolone-induced rash

​

(Answer on next page)

Diagnosis: Henoch-Schönlein purpura (A)

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children,¹ but it also occurs in adults. HSP is an inflammatory disorder characterized by antigen-antibody (immunoglobulin A [IgA]) immune complexes in the smaller venules, capillaries, and arterioles.² Although the exact cause is unknown, HSP has been associated with bacterial and viral infections, medications, insect bites, and vaccinations, among other factors.^2-4

Because HSP tends to be a self-limited disease, the true incidence is thought to be underreported, but in adults, the incidence is estimated to range between 3.4 and 14.3 per million persons.³ Typical clinical presentations of HSP include palpable purpura, abdominal pain, arthritis, and hematuria.² Some reports have noted HSP to have a seasonal correlation, but this varies throughout the literature, with some reports indicating a higher prevalence in the spring and others in the fall or winter.² Regardless of when it occurs, HSP frequently follows an infection of the throat or breathing passages.² 

HSP skin lesions are typically located on the lower extremities and buttocks, but they may also appear on the hands, forearms, and legs, particularly on the extensor surfaces.² Purpuric areas may progress from red to purple, or rust-colored, and then fade, but in severe cases, hemorrhagic or necrotic lesions may appear more prominently.² The diagnosis of HSP is straightforward when patients present with the classic signs and symptoms, especially palpable purpura of the lower extremities and buttocks. In patients with incomplete or unusual presentations, like the case patient, who presented with a nonpurpuric rash, a biopsy of an affected organ (eg, skin or kidney) that demonstrates leukocytoclastic vasculitis with a predominance of IgA deposition confirms the diagnosis of HSP. 

Abdominal pain is a common symptom of gastrointestinal (GI) involvement in vasculitis, but skin manifestations usually precede GI symptoms.^2,3 Children tend to have more frequent and more serious GI symptoms, whereas adults more often experience renal involvement.⁴ Between 20% and 50% of patients with HSP have some degree of renal involvement,⁵ which typically occurs within 3 months of the onset of the rash.³ Hematuria and proteinuria are the most common signs of renal involvement, and although they often resolve on their own, in rare cases, chronic renal disease can develop.³ 

Case Patient Outcome 

In our patient, further work-up showed an elevated IgA level and nephritic range proteinuria. A dermatologist saw the patient, but a skin biopsy was determined to be of low yield, as there were no fresh lesions on the skin at the time. Due to the renal involvement, the patient was treated with a course of prednisone, which resulted in dramatic improvement in his skin lesions and complete resolution of hematuria in 1 week.  

Differential Diagnosis of HSP 

The differential diagnosis of HSP may include idiopathic thrombocytopenic purpura, poststreptococcal glomerulonephritis, and flouroquinolone-induced rash. A clinical diagnosis of HSP may be obvious if the patient has concomitant rash, GI symptoms or hematuria, and arthritis,² a triad of symptoms indicative of HSP based on the 2006 diagnostic criteria established by the European League Against Rheumatism and the Pediatric Rheumatology European Society.⁶ However, a diagnostic challenge may arise if patients have only one or two of the common symptoms. In such cases, a combination of blood tests, urine tests, skin biopsy, kidney biopsy, and imaging studies may be necessary to rule out other diseases. 

Idiopathic thrombocytopenic purpura (ITP). ITP is a hemotologic disorder in which the immune system destroys platelets, impairing normal blood clotting. Symptoms of ITP include easy bruising, nosebleeds or bleeding in the mouth, and a petechial rash.⁷ A complete blood count reveals thrombocytopenia, and a peripheral smear confirms few platelets. In our case patient, the complete blood count documented a normal platelet count. ITP is rarely associated with renal failure.⁸

Poststreptococcal glomerulonephritis. This kidney disorder is often caused by infection with nephritogenic group A beta-hemolytic streptococci. It often appears after pharyngitis or impetigo, with onset 1 to 3 weeks after infection—unlike HSP, in which the lag period is much shorter, with onset after just a few days (this is known as synpharyngitic hematuria).⁹ Symptoms of poststreptococcal glomerulonephritis include rust-colored urine, hematuria, and edema of the abdomen, face, feet, and ankles.¹⁰ Joint pain may also occur. Skin findings of this condition may appear different with impetigo lesions, unlike the diffuse dependent rash that is characteristic of HSP. A biopsy of the kidney would confirm the diagnosis by revealing segmental glomerulonepritis with crescents and mesangial IgA desposition. 

Fluoroquinolone-induced vasculitis. Fluoroquinolones are generally well-tolerated antibiotics, but their side effects may include central nervous system and GI disturbances, and dermatologic adverse effects, which occur at a rate of 0.5% to 3%.¹¹ Rare adverse dermatologic effects include photosensitivity, vasculitis, and HSP. Unspecified rashes have been most frequent. A flouroquinolone-induced rash also tends to be generalized and is rarely associated with hematuria and kidney involvement.² Acute interstitial nephritis also occurs infrequently with the use of flouroquinolones and is associated with elevated eosinophils.¹² Our case patient was treated with flouroquinolones in the past, but his treatment was not associated with the skin rashes.

Approaches to Treatment 

Because HSP tends to be self-limited, pharmacological treatment for HSP is often not recommended, except in the presence of renal disease and central nervous system involvement.² Symptomatic treatment can be used for rash and arthritis. Prednisone 1 mg/kg daily may benefit adults and children with severe extrarenal manifestations and with kidney disease.¹³ 

References

1. Drug allergy. Leung D YM, Sampson H, Geha R, Szefler SJ, eds. Pediatric Allergy: Principles & Practices. 2nd ed. New York, NY: Saunders Elsevier; 2010.

2. Kraft DM, Mckee D, Scott C. Henoch-Schönlein purpura: a review. Am Fam Physician. 1998;58(2):405-408, 411.

3. Sohagia AB, Gunturu SG, Tong TR, Hertan HI. Henoch-Schonlein purpura—a case report and review of the literature. Gastroenterol Res Pract. 2010:597648.

4. Mayo Clinic. Henoch-Schonlein purpura. Symptoms. www.mayoclinic.com/health/henoch-schonlein-purpura/DS00838/DSECTION=symptoms. Published November 4, 2010. Accessed October 23, 2012.

5. Mills JA, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum. 1990;33(8):1114-1121.

6. Ozen S, Ruperto N, Dillon MJ, et al. EURLAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis. 2006;65(7):936-941.

7. Idiopathic thrombocytopenic purpura. Penn State Hershey Milton S. Hershey Medical Center Website. https://pennstatehershey.adam.com/content.aspx?productId=112&pid=1&gid=000535. Reviewed March 28, 2010. Accessed October 23, 2012.

8. Cines DB, McMillan R. Management of adult idiopathic thrombocytopenic purpura. Annu Rev Med. 2005;56:425-442.

9. Nachman PH, Jennette JC, Falk RJ. Primary glomerular disease. In: Brenner BM, ed. Brenner and Rector's The Kidney. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2008.

10. Post-streptococcal glomerulonephritis. Medline Plus. www.nlm.nih.gov/medlineplus/ency/article/000503.htm. Updated September 20, 2011. Accessed October 23, 2012.

11. Antony SJ, Soto-Ruiz E. Unusual cutaneous manifestations of quinolone therapy. Internet J Infect Dis. 2010;8(2).

12. Hung CC, Kuo MC, Chang JM, Chen HC. Flouroquinolone-induced acute interstitial nephritis in immunocompromised patients: two case reports. Nephrol Dial Transplant. 2006;21(1):237-238.

13. Weiss PF, Feinstein JA, Luan X, Burnham JM, Feudtner C. Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review. Pediatrics. 2007;120(5):1079-1087.