30 May 2023: Articles
Unusual clinical course, Challenging differential diagnosis, Diagnostic / therapeutic accidents, Unusual setting of medical care, Adverse events of drug therapy , Clinical situation which can not be reproduced for ethical reasonsKateryna Strubchevska 1CDEF*, Marko Kozyk 1DEF, Dinu V. Balanescu 1DEF
Am J Case Rep 2023; 24:e939541
BACKGROUND: Leukocytoclastic vasculitis is a small-vessel vasculitis associated with infections, autoimmune disorders, and certain drugs, but it may also be idiopathic.
CASE REPORT: We report the case of a 37-year-old woman with no significant past medical history who presented with a chief concern of a full-body rash. Before the rash appeared, she had been treated for group A Streptococcus with amoxicillin and prednisone. An outpatient skin biopsy revealed findings concerning for early leukocytoclastic vasculitis. On admission, she had a diffuse palpable rash on the trunk and upper and lower extremities. Laboratory test results were notable for neutrophilic leukocytosis with a left shift, reticulocytosis with normal hemoglobin, thrombocytosis, and elevated ESR and CRP. An infectious diseases workup was negative, serum levels of complement C3 and C4 were normal, and no evidence of hemolysis was found on blood smear. Results of schistocytes review, LDH, and haptoglobin were not consistent with hemolysis, and IgG, IgA, and IgM were all within normal limits. The patient was initially started on antibiotics due to concern for bullous impetigo, but the treatment regimen was changed to steroids because IgA vasculitis and leukocytoclastic vasculitis were suspected. Biopsy results were received 1 week later and did not reveal definitive findings of acute leukocytoclastic vasculitis. Staining with antibodies to human IgG, IgA, IgM, C3, fibrinogen, and albumin was negative.
CONCLUSIONS: Leukocytoclastic vasculitis can be triggered by penicillins, cephalosporins, sulfonamides, phenytoin, and allopurinol acting as haptens and stimulating an immune response, resulting in development of vasculitis.
Keywords: Vasculitis, Leukocytoclastic, Cutaneous, Vasculitis, Lymphocytic, Cutaneous Small Vessel, Haptens
Leukocytoclastic vasculitis is a small-vessel vasculitis associated with infections, autoimmune disorders, and certain drugs, but it can also be idiopathic. Common clinical features include purpuric rash, predominantly on the lower extremities. Rarely, extracutaneous manifestations such as low-grade fever, malaise, weight loss, myalgias, and arthralgias can develop. Symptoms spontaneously improve in most cases. In severe or prolonged cases, treatment with steroids and steroid-sparing agents should be considered .
This is a 37-year-old woman with no significant past medical history presented with a chief concern of a full-body rash, which started on the medial aspect of her thighs bilaterally 2 weeks prior to presentation. The rash initially presented as small petechiae, which subsequently enlarged and spread down the trunk and the upper and lower extremities (Figure 1). Some lesions were coalescing and developed ulcerated blisters. The day after the rash appeared, she presented to an urgent care clinic due to associated sore throat and subjective fever. She tested positive for group A Streptococcus and was prescribed an oral course of amoxicillin-clavulanate 875-125 mg as well as prednisone 40 mg daily. She was compliant with this regimen, without improvement of her rash. An outpatient skin biopsy was performed just before the admission, which revealed findings concerning for early leukocytoclastic vasculitis, but no direct immunofluorescence was performed. Home medications included diphenhydramine, cetirizine, ibuprofen, and prednisolone. A physical exam was remarkable for diffuse palpable rash on the trunk and on the upper and lower extremities. Laboratory tests results were notable for neutrophilic leukocytosis up to 21.9 bil/L with a left shift, reticulocytosis with a normal hemoglobin, thrombocytosis, elevated ESR, and CRP. Test results for HIV, hepatitis B, hepatitis C, MPO-ANCA, PR3-ANCA, ANA, DNA-ASE B, cryoglobulin, and streptolysin O antibodies were negative. Serum levels of complement C3 and C4 were normal. Ferritin and iron studies were within normal limits. Folate and B12 were both low but MCV was normal. No evidence of hemolysis was found on blood smear; schistocytes review, LDH, and haptoglobin were not consistent with hemolysis. IgG, IgA, and IgM were all within normal limits. Urinalysis was normal. She was initially started on vancomycin due to concern for bullous impetigo; however, vancomycin was subsequently discontinued, and clindamycin was started. She was also started on intravenous steroids, followed by transition to oral prednisone. IgA vasculitis and leukocytoclastic vasculitis were suspected. Biopsy results were received 1 week later and did not reveal definitive findings of an acute leukocytoclastic vasculitis. Staining with antibodies to human IgG, IgA, IgM, C3, fibrinogen, and albumin was negative.
The patient improved clinically and was discharged on clindamycin and prednisone taper. She was also started on folate and vitamin B12 supplementation. The patient was recommended to follow up in a clinic and monitor for any signs of rash progression.
Cutaneous vasculitis is an inflammation of the small dermal blood vessel walls without systemic vasculitis or glomerulonephritis . Since the vasculitis usually involves small superficial vessels, urticaria, plaques, papules, and palpable purpura are commonly seen. In addition, inflammation can spread to the vessels of the dermo-hypodermic junction and may result in ulcers, nodules, or livedo. To investigate the type of inflammatory infiltrate and establish the final diagnosis, a skin biopsy should be performed. Leukocytoclastic vasculitis is a common manifestation of other vasculitides presenting with similar skin lesions .
Cutaneous lesions can develop in many systemic small vessel vasculitides such as cryoglobulinemic vasculitis, Henoch-Schönlein purpura (IgA vasculitis), antineutrophil cytoplasmic antibody-associated vasculitis, and infectious endocarditis. Therefore, it is reasonable to regard leukocytoclastic vasculitis as an “umbrella term” for many diseases.
Medications such as penicillins, cephalosporins, sulfonamides, phenytoin, biological agents, particularly the anti-TNF-α molecules , and allopurinol may act as haptens and stimulate an immune response triggering the development of vasculitis. Cutaneous small-vessel vasculitis may also develop in the settings of infections such as hepatitis B or C, HIV, infective endocarditis, and infected shuts .
During evaluation of a case suspicious for vasculitis skin lesions, comprehensive history and physical examination are important to determine whether the disease is limited to the skin. Complete blood count, complete metabolic panel, urinalysis, blood cultures, and immunologic screening (antineutrophil cytoplasmic antibodies, levels of the complement components C3 and C4, anti-nuclear antibodies, extractable nuclear antigens panel, cryoglobulins, anti-C1-q antibodies, testing for hepatitis B and C) must be ordered due to a very broad differential diagnosis. Imaging studies depend on the individual patient’s presentation . Cutaneous biopsy from the newest lesion and direct immunofluorescence testing are conducted to confirm the diagnosis.
In our case, the patient developed purpura and tense bullae on her extremities and lower trunk, but no rash was present on the upper trunk and face. In addition, there was a documented history of amoxicillin-clavulanate use secondary to group A streptococcal pharyngitis as well as regular intake of nonsteroidal anti-inflammatory drugs. The patient did not have any systemic symptoms such as fever, hematuria, abdominal pain, or diarrhea; therefore, the disease most likely was limited to the skin.
Initial treatment of leukocytoclastic vasculitis includes discontinuation of possible offending medications (non-steroidal anti-inflammatory drugs in our case). If cutaneous manifestations are severe, the patient can be started on steroids, immunosuppressants, or rituximab based on the severity of presentation. In our case, we treated the patient only with steroids. Therapeutic plasma-exchange is performed in complicated cases. In some cases, when the lesions are limited to the skin, only symptomatic treatment is needed .
Leukocytoclastic vasculitis is a small-vessel vasculitis associated with infections, autoimmune disorders, and certain drugs; however, it may also be idiopathic. Common manifestations include cutaneous lesions, and biopsy is required to establish a final diagnosis. Treatment includes prompt discontinuation of the offending medications as well as initiation of steroids, immunosuppressants, or rituximab based on the severity of presentation.
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