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Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.1 Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.2 Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

 

 

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.3

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.4

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.5 Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.6 Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.7 Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.8

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

References

1. Gaurav K, Keith RM. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3): 495-520. doi:10.1016/j.hoc.2013.03.001

2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.

3. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Saunders/Elsevier; 2011.

4. Einhorn J, Levis JT. Dermatologic diagnosis: leukocytoclastic vasculitis. Perm J. 2015;19(3):77-78. doi:10.7812/TPP/15-001

5. The role of infectious agents in the pathogenesis of vasculitis. Nicolò P, Carlo S. Best Pract Res Clin Rheumatol. 2008;22(5):897-911. doi:10.7812/TPP/15-001

6. Maunz G, Conzett T, Zimmerli W. Cutaneous vasculitis associated with fluoroquinolones. Infection. 2009;37(5):466-468. doi:10.1007/s15010-009-8437-4

7. Baigrie D, Goyal A, Crane J.C. Leukocytoclastic vasculitis. StatPearls [internet]. Updated May 8, 2022. Accessed October 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK482159

8. Micheletti RG, Pagnoux C. Management of cutaneous vasculitis. Presse Med. 2020; 49(3):104033. doi:10.1016/j.lpm.2020.104033

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Saria Tasnim, MDa; Hina Yousuf, MDa; Yasir Al-Hilli, MDa; Waqas Rasheed, MDa; Kaylee Shepherd, MDa 
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Sara Tasnim (sariatasnimsneha20@ gmail.com)

aTexas Tech University Health Sciences Center, Lubbock

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aTexas Tech University Health Sciences Center, Lubbock

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The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Ethics and consent

No informed consent was obtained from the patient; patient identifiers were removed to protect the patient’s identity.

Author and Disclosure Information

Saria Tasnim, MDa; Hina Yousuf, MDa; Yasir Al-Hilli, MDa; Waqas Rasheed, MDa; Kaylee Shepherd, MDa 
Correspondence:
Sara Tasnim (sariatasnimsneha20@ gmail.com)

aTexas Tech University Health Sciences Center, Lubbock

Author disclosures

The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Ethics and consent

No informed consent was obtained from the patient; patient identifiers were removed to protect the patient’s identity.

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Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.1 Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.2 Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

 

 

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.3

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.4

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.5 Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.6 Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.7 Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.8

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated acquired condition affecting both adults and children.1 Acute ITP is the most common form, which happens in the presence of a precipitant, leading to a drop in platelet counts. However, chronic ITP can occur when all the causes that might precipitate thrombocytopenia have been ruled out, and it is persistent for ≥ 12 months.2 Its presence can mask other diseases that exhibit somewhat similar signs and symptoms. We present a case of a patient presenting with chronic ITP with diffuse rash and was later diagnosed with idiopathic leukocytoclastic vasculitis (LCV).

Case Presentation

A 79-year-old presented to the hospital with 2-day history of a rash. The rash was purpureal and petechial and located on the trunk and bilateral upper and lower extremities. The rash was associated with itchiness and pain in the wrists, ankles, and small joints of the hands. The patient reported no changes in medication or diet, no recent upper respiratory tract or gastrointestinal infections, fever or chills, night sweats, or weight loss. The patient’s medical history consisted of thrombocytopenia about 5 years before and since then had been following up with a hematologist and underwent an extensive workup, including bone marrow biopsy without a definite diagnosis.

The patient mentioned that at the time of diagnosis the platelet count was about 90,000 but had been fluctuating between 50 and 60,000 recently. The patient also reported no history of gum bleeding, nosebleeds, hemoptysis, hematemesis, or any miscarriages. She also had difficulty voiding for 2 to 3 days but no dysuria, frequency, urgency, or incontinence.

The patient was diagnosed with a urinary tract infection (UTI) 1 day before presentation and was started on ciprofloxacin 500 mg daily for 5 days. Her home medications included diphenhydramine as needed, metoprolol, and levothyroxine 125 µg. Her medical history was significant for hypertension, bradycardia with pacemaker placement, and obstructive sleep apnea. There were no noteworthy elements in her family and social history.

Laboratory results were significant for 57,000/µL platelet count (normal range, 150,000-450,000), elevated d-dimer (6.07), < 6 mg/dL C4 (normal range, 88-201). Hemoglobin level, coagulation panel, hemolytic panel, and fibrinogen level results were unremarkable. The hepatitis panel, Lyme disease, and HIV test were negative. The peripheral blood smear showed moderate thrombocytopenia, mild monocytosis, and borderline normochromic normocytic anemia without schistocytes. The autoimmune panel to evaluate thrombocytopenia showed platelet antibody against glycoprotein (GP) IIb/IIIa, GP Ib/Ix, GP Ia/IIa, suggestive toward a diagnosis of chronic idiopathic ITP. However, the skin biopsy of the rash was indicative of LCV.

An autoimmune panel for vasculitis, including antinuclear antibody and antidouble-stranded DNA, was negative. While in the hospital, the patient completed the course of ciprofloxacin for the UTI, the rash started to fade without any intervention, and the platelet count improved to 69,000/µL. The patient was discharged after 3 days with the recommendation to follow up with her hematologist.

 

 

Discussion

LCV is a small vessel vasculitis of the dermal capillaries and venules. Histologically, LCV is characterized by fibrinoid necrosis of the vessel wall with frequent neutrophils, nuclear dust, and extravasated erythrocytes.3

Although a thorough evaluation is recommended to determine etiology, about 50% of cases are idiopathic. The most common precipitants are acute infection or a new medication. Postinfectious LCV is most commonly seen after streptococcal upper respiratory tract infection. Among other infectious triggers, Mycobacterium, Staphylococcus aureus, chlamydia, Neisseria, HIV, hepatitis B, hepatitis C, and syphilis are noteworthy. Foods, autoimmune disease, collagen vascular disease, and malignancy are also associated with LCV.4

In our patient we could not find any specific identifiable triggers. However, the presence of a UTI as a precipitating factor cannot be ruled out.5 Moreover, the patient received ciprofloxacin and there have been several case reports of LCV associated with use of a fluroquinolone.6 Nevertheless, in the presence of chronic ITP, which also is an auto-immune condition, an idiopathic cause seemed a reasonable explanation for the patient’s etiopathogenesis.

The cutaneous manifestations of LCV may appear about 1 to 3 weeks after the triggering event if present. The major clinical findings include palpable purpura and/or petechiae that are nonblanching. These findings can easily be confused with other diagnoses especially in the presence of a similar preexisting diagnosis. For example, our patient already had chronic ITP, and in such circumstances, a diagnosis of superimposed LCV can be easily missed without a thorough investigation. Extracutaneous manifestations with LCV are less common. Systemic symptoms may include low-grade fevers, malaise, weight loss, myalgia, and arthralgia. These findings have been noted in about 30% of affected patients, with arthralgia the most common manifestation.7 Our patient also presented with pain involving multiple joints.

The mainstay of diagnosis for LCV is a skin biopsy with direct immunofluorescence. However, a workup for an underlying condition should be considered based on clinical suspicion. If a secondary cause is found, management should target treating the underlying cause, including withdrawal of the offending drug, treatment or control of the underlying infection, malignancy, or connective tissue disease. Most cases of idiopathic cutaneous LCV resolve with supportive measures, including leg elevation, rest, compression stockings, and antihistamines. In resistant cases, a 4- to 6-week tapering dose of corticosteroids and immunosuppressive steroid-sparing agents may be needed.8

Conclusions

Although most cases of LCV are mild and resolve without intervention, many cases go undiagnosed due to a delay in performing a biopsy. However, we should always look for the root cause of a patient’s condition to rule out underlying contributing conditions. Differentiating LCV from any other preexisting condition presenting similarly is important.

References

1. Gaurav K, Keith RM. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3): 495-520. doi:10.1016/j.hoc.2013.03.001

2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.

3. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Saunders/Elsevier; 2011.

4. Einhorn J, Levis JT. Dermatologic diagnosis: leukocytoclastic vasculitis. Perm J. 2015;19(3):77-78. doi:10.7812/TPP/15-001

5. The role of infectious agents in the pathogenesis of vasculitis. Nicolò P, Carlo S. Best Pract Res Clin Rheumatol. 2008;22(5):897-911. doi:10.7812/TPP/15-001

6. Maunz G, Conzett T, Zimmerli W. Cutaneous vasculitis associated with fluoroquinolones. Infection. 2009;37(5):466-468. doi:10.1007/s15010-009-8437-4

7. Baigrie D, Goyal A, Crane J.C. Leukocytoclastic vasculitis. StatPearls [internet]. Updated May 8, 2022. Accessed October 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK482159

8. Micheletti RG, Pagnoux C. Management of cutaneous vasculitis. Presse Med. 2020; 49(3):104033. doi:10.1016/j.lpm.2020.104033

References

1. Gaurav K, Keith RM. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3): 495-520. doi:10.1016/j.hoc.2013.03.001

2. Rodeghiero F, Stasi R, Gernsheimer T, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood. 2009;113(11):2386-2393.

3. James WD, Berger TG, Elston DM. Andrews’ Diseases of the Skin: Clinical Dermatology. 11th ed. Saunders/Elsevier; 2011.

4. Einhorn J, Levis JT. Dermatologic diagnosis: leukocytoclastic vasculitis. Perm J. 2015;19(3):77-78. doi:10.7812/TPP/15-001

5. The role of infectious agents in the pathogenesis of vasculitis. Nicolò P, Carlo S. Best Pract Res Clin Rheumatol. 2008;22(5):897-911. doi:10.7812/TPP/15-001

6. Maunz G, Conzett T, Zimmerli W. Cutaneous vasculitis associated with fluoroquinolones. Infection. 2009;37(5):466-468. doi:10.1007/s15010-009-8437-4

7. Baigrie D, Goyal A, Crane J.C. Leukocytoclastic vasculitis. StatPearls [internet]. Updated May 8, 2022. Accessed October 10, 2022. https://www.ncbi.nlm.nih.gov/books/NBK482159

8. Micheletti RG, Pagnoux C. Management of cutaneous vasculitis. Presse Med. 2020; 49(3):104033. doi:10.1016/j.lpm.2020.104033

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