Cutaneous polyarteritis nodosa presenting as a solitary blue toe
Authors: Amanda Joy Tschetter, Vincent Liu, Karolyn A. Wanat
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A woman in her 30s with a history of Crohn disease, quiescent on mesalamine, presented with a 1-year history of mild purple discoloration of the left great toe, which progressed to painful, burning nodules limiting movement of the digit. Her symptoms did not fluctuate with changing temperatures. She smoked less than 1 pack of cigarettes daily, but denied alcohol or drug use. Her only other medication was paroxetine. Numerous oral antibiotics and antifungals were previously ineffective. Prior arterial Doppler ultrasound was normal; magnetic resonance imaging demonstrated chronic degenerative arthritic changes.Physical examination demonstrated multiple tender subcutaneous nodules of the left hallux with background violaceous discoloration and edema limited to the toe (Fig 1). She was afebrile. Feet were warm with intact sensation and pulses. Punch biopsy showed medium vessel vasculitis (Fig 2) consistent with polyarteritis nodosa (PAN). Tissue cultures were negative. Complete blood count, complete metabolic panel, urinalysis, antinuclear antibody, rheumatoid factor, complements III/IV, human immunodeficiency virus, and hepatitis panels were normal. Prednisone 40 mg daily was initiated with disease resolution, but pain and edema returned at the end of the 6-week taper. Ibuprofen 600 mg every 6 hours was initiated with improvement.Fig 2Cutaneous polyarteritis nodosa presenting as a solitary blue toe. Histopathologic specimen reveals a neutrophilic infiltrate obliterating a medium-sized blood vessel wall in the deep dermis consistent with a medium vessel vasculitis. (Hematoxylin-eosin stain; original magnification: ×20.)View Large Image Figure ViewerDownload Hi-res image Download (PPT)We present a case of cutaneous polyarteritis nodosa (cPAN) presenting as a solitary, painful, violaceous toe. Blue toe syndrome (BTS), named for the physical finding of a violaceous toe in the absence of trauma, cold-induced injury, or generalized cyanosis, has numerous etiologies including emboli, thromboses, vasoconstriction, infections, and inflammatory disorders.1Hirschmann J.V. Raugi G.J. Blue (or purple) toe syndrome.J Am Acad Dermatol. 2009; 60: 1-22Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Importantly, vasculitis can lead to BTS, including a case of granulomatosis with polyangiitis presenting as a single, tender, violaceous toe 5 months before the onset of any systemic symptoms.2Begon E. Bouilly P. Cheysson E. Cohen P. Bachmeyer C. Isolated blue toe syndrome as the initial sign of Wegener granulomatosis.Am J Med. 2010; 123: e7-e8Abstract Full Text Full Text PDF PubMed Scopus (4) Google ScholarcPAN, considered a benign variant of polyarteritis nodosa (PAN), is frequently seen in association with inflammatory disorders, infections, and medications.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar It often presents as tender subcutaneous nodules on the lower extremities, with associated ulceration, livedo reticularis, petechiae, purpura, digital necrosis, and autoamputation. Women are commonly affected with a peak incidence in middle age.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar cPAN typically remains localized to the skin, follows a chronic, relapsing and remitting course, and, conventionally, does not progress to systemic PAN. If present, extracutaneous manifestations (arthralgias, myalgias, neuropathy) should remain localized to the region of affected skin.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google ScholarInflammatory bowel disease has been reported in approximately 6% of cPAN cases,3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar generally precedes the cPAN diagnosis, and is more likely associated with Crohn disease (CD) than ulcerative colitis.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Flare in one disease does not predict poor control in the other.4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Since the initial report in 1970, fewer than 25 cases of cPAN associated with CD have been reported.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar, 5Magnant J. Lhommet C. Machet L. Machet M.C. Guilmot J.L. Diot E. [Cutaneous polyarteritis nodosa and Crohn's disease: an association not to be ignored].Rev Med Interne. 2009; 30: 345-348Crossref PubMed Scopus (6) Google Scholar Most recently, a report of 2 women with CD presented with subcutaneous nodules, edema, livedo reticularis, and Raynaud type symptoms. One woman had longstanding, quiescent CD before onset of cPAN, which required cyclophosphamide and ultimately led to amputation of a toe; the second had a banal cPAN course controlled by a slow taper of prednisone with onset of symptoms around the time of her CD diagnosis. As in our patient, cPAN is generally responsive to corticosteroids.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Nonsteroidal anti-inflammatory medications may be useful for prevention and treatment of mild flares and were successfully employed in our patient.We present an instructive case of cPAN presenting as a solitary blue toe to make clinicians aware of this unusual presentation in order to facilitate initiation of appropriate work-up and therapy. To the Editor: A woman in her 30s with a history of Crohn disease, quiescent on mesalamine, presented with a 1-year history of mild purple discoloration of the left great toe, which progressed to painful, burning nodules limiting movement of the digit. Her symptoms did not fluctuate with changing temperatures. She smoked less than 1 pack of cigarettes daily, but denied alcohol or drug use. Her only other medication was paroxetine. Numerous oral antibiotics and antifungals were previously ineffective. Prior arterial Doppler ultrasound was normal; magnetic resonance imaging demonstrated chronic degenerative arthritic changes. Physical examination demonstrated multiple tender subcutaneous nodules of the left hallux with background violaceous discoloration and edema limited to the toe (Fig 1). She was afebrile. Feet were warm with intact sensation and pulses. Punch biopsy showed medium vessel vasculitis (Fig 2) consistent with polyarteritis nodosa (PAN). Tissue cultures were negative. Complete blood count, complete metabolic panel, urinalysis, antinuclear antibody, rheumatoid factor, complements III/IV, human immunodeficiency virus, and hepatitis panels were normal. Prednisone 40 mg daily was initiated with disease resolution, but pain and edema returned at the end of the 6-week taper. Ibuprofen 600 mg every 6 hours was initiated with improvement. We present a case of cutaneous polyarteritis nodosa (cPAN) presenting as a solitary, painful, violaceous toe. Blue toe syndrome (BTS), named for the physical finding of a violaceous toe in the absence of trauma, cold-induced injury, or generalized cyanosis, has numerous etiologies including emboli, thromboses, vasoconstriction, infections, and inflammatory disorders.1Hirschmann J.V. Raugi G.J. Blue (or purple) toe syndrome.J Am Acad Dermatol. 2009; 60: 1-22Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar Importantly, vasculitis can lead to BTS, including a case of granulomatosis with polyangiitis presenting as a single, tender, violaceous toe 5 months before the onset of any systemic symptoms.2Begon E. Bouilly P. Cheysson E. Cohen P. Bachmeyer C. Isolated blue toe syndrome as the initial sign of Wegener granulomatosis.Am J Med. 2010; 123: e7-e8Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar cPAN, considered a benign variant of polyarteritis nodosa (PAN), is frequently seen in association with inflammatory disorders, infections, and medications.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar It often presents as tender subcutaneous nodules on the lower extremities, with associated ulceration, livedo reticularis, petechiae, purpura, digital necrosis, and autoamputation. Women are commonly affected with a peak incidence in middle age.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar cPAN typically remains localized to the skin, follows a chronic, relapsing and remitting course, and, conventionally, does not progress to systemic PAN. If present, extracutaneous manifestations (arthralgias, myalgias, neuropathy) should remain localized to the region of affected skin.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar Inflammatory bowel disease has been reported in approximately 6% of cPAN cases,3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar generally precedes the cPAN diagnosis, and is more likely associated with Crohn disease (CD) than ulcerative colitis.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Flare in one disease does not predict poor control in the other.4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Since the initial report in 1970, fewer than 25 cases of cPAN associated with CD have been reported.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar, 5Magnant J. Lhommet C. Machet L. Machet M.C. Guilmot J.L. Diot E. [Cutaneous polyarteritis nodosa and Crohn's disease: an association not to be ignored].Rev Med Interne. 2009; 30: 345-348Crossref PubMed Scopus (6) Google Scholar Most recently, a report of 2 women with CD presented with subcutaneous nodules, edema, livedo reticularis, and Raynaud type symptoms. One woman had longstanding, quiescent CD before onset of cPAN, which required cyclophosphamide and ultimately led to amputation of a toe; the second had a banal cPAN course controlled by a slow taper of prednisone with onset of symptoms around the time of her CD diagnosis. As in our patient, cPAN is generally responsive to corticosteroids.3Daoud M.S. Hutton K.P. Gibson L.E. Cutaneous periarteritis nodosa: a clinicopathological study of 79 cases.Br J Dermatol. 1997; 136: 706-713Crossref PubMed Scopus (190) Google Scholar, 4Komatsuda A. Kinoshita K. Togashi M. Maki N. Masai R. Niitsu H. et al.Cutaneous polyarteritis nodosa in a patient with Crohn's disease.Mod Rheumatol. 2008; 18: 639-642Crossref PubMed Google Scholar Nonsteroidal anti-inflammatory medications may be useful for prevention and treatment of mild flares and were successfully employed in our patient. We present an instructive case of cPAN presenting as a solitary blue toe to make clinicians aware of this unusual presentation in order to facilitate initiation of appropriate work-up and therapy.