|CASE BASED REVIEW
|Ahead of print publication
Peripheral limb gangrene in a child with polyarteritis nodosa: An unusual presentation
Namrata Patil, Murtuja Shaikh, Alpana Kondekar, Surabhi Rathi, Karishma Bade, Suroor Makharia
Department of Pediatrics, TNMC and BYL Nair Hospital, Mumbai, Maharashtra, India
|Date of Submission||28-Jun-2021|
|Date of Acceptance||07-Sep-2021|
|Date of Web Publication||10-May-2022|
Department of Pediatrics, TNMC and BYL Nair Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Polyarteritis nodosa (PAN) is a necrotizing vasculitis predominantly affecting medium-sized muscular arteries. PAN is comparatively rarer in childhood. It can present either in the form of cutaneous lesions (c-PAN) or systemic involvement (classic PAN). Classic PAN involves multiorgan system whereas cutaneous PAN has benign, chronic and relapsing course characterized by involvement of skin, muscles, and joints. PAN presenting as gangrene of peripheral limbs is a rare presentation. Very few cases have been reported in the Indian Pediatrics literature. Here, we report a case of peripheral limb gangrene presenting as the initial manifestation of PAN.
Keywords: Gangrene, polyarteritis nodosa, vasculitis
| Introduction|| |
Childhood vasculitis is a complex and rare condition which often requires multidisciplinary care. Arriving to the diagnosis can be challenging as the symptoms are acute and nonspecific. Fever with elevated inflammatory markers might be the only clue to suggest systemic vasculitis. Polyarteritis nodosa PAN is a rare type of vasculitis in children which can be missed as arterial biopsy not being readily available prevents confirmation of diagnosis in case of mimics. Due to the rarity of childhood PAN, there are no widely accepted evidence-based treatment recommendations. PAN has varying presentations from a benign cutaneous form to severe life- and limb-threatening form.
| Case Report|| |
A 10-year-old male, immunized for age, presented with a complaint of on-and-off fever with intermittent, stabbing pain over the right toe for 10–15 days, following which he developed blackish discoloration of the right toe and sole. There was no significant history of trauma, joint pain, abdominal pain, and rash. On examination, the temperature was 39°C, tachycardia 120/min, and normal blood pressure 104/70 mmHg. Dorsalis pedis pulse was absent over the right foot. There was blackish discoloration about 1.5 cm × 1.5 cm over the right toe and sole [Figure 1]. Line of demarcation was not there. Systemic examination was normal. His investigations showed the following results: hemoglobin: 8.5 g/dl, total leukocyte count: 24,700 cells/cumm, and platelet count: 7.8 × 109/L. There was normocytic normochromic anemia on peripheral smear. Liver and renal function tests were normal. Prothrombin time (15.5 s) and activated partial thromboplastin time (36.45 s) were normal. Sickling test was negative. His fasting lipid profile (cholesterol: 255 mg/dl and triglycerides: 187 mg/dl) and homocysteine level (4.7 μm/L) were normal. The inflammatory markers were raised. C-reactive protein (CRP) was 250 mg/dl and erythrocyte sedimentation rate (ESR) was 100 mm in the 1st h. Hepatitis B surface antigen was negative. Our differentials were Prothrombotic disease and sepsis leading to thrombus formation. Blood culture was negative. Doppler of the limb was suggestive of complete lumen occluding thrombus of the distal right posterior tibial artery. He was started on low-molecular-weight heparin. However, the child continued to have fever spikes, and there was progression of thrombus. Covid antibodies were negative and 2D echo was normal which ruled out covid as prothrombotic state leading to gangrene. Protein C, protein S, Factor V Leiden mutation, Anticardiolipin IgG, IgM) and ds-DNA were negative, which ruled out prothrombotic condition as the etiology. Antineutrophil cytoplasmic antibodies (p-ANCA and c-ANCA) were negative. Persistent high counts, fever unresponsive to antibodies and high platelets suggested ongoing inflammation or vasculitis as cause. Based on acute-onset peripheral gangrene, leukocytosis, thrombocytosis, negative autoantibodies, elevated ESR, and CRP, a provisional diagnosis of PAN was made. He was then started on intravenous methylprednisolone for 3 consecutive days. He had a marked relief in pain with reduction in fever spikes by the 2nd day. Due to practical limitations, histopathology and visceral angiography could not be done. Skin biopsy was suggestive of confluent necrosis of epidermis with multiple dilated blood vessels with eosinophilic and lymphocytic infiltrate in vascular lamina which was consistent with vasculopathy. Further, he was treated with pulse intravenous cyclophosphamide (500 mg/m2) and oral prednisolone. There was no further progression of gangrene and line of demarcation was formed over the right toe [Figure 2] for which below-knee amputation was done and was given pylon prosthesis for the same. He was followed up regularly and was in remission on prednisolone.
| Discussion|| |
Kussmaul and Maier first described PAN in 1866. There are very few case reports documented in children. The pathologic features of cutaneous PAN are at the dermal pannicular junction showing fibrinoid degeneration involving all layers of the vessel wall with infiltration of inflammatory cells, mainly neutrophil, eosinophil, lymphocytes, and plasma cells in the wall. Livedo reticularis, purpura, subcutaneous nodules, and skin infarctions are usual skin findings in PAN. In our case, since the child directly presented with gangrene, the above features were not noted. Symmetric involvement is an important indication in the identification that the cause of the skin necrosis is most likely from vasculopathy rather than emboli. The classification criteria for a diagnosis of systemic PAN in childhood include either histopathologic evidence of necrotizing vasculitis in medium-sized arteries or angiographic abnormality of a medium or small artery as a compulsory criterion plus one of the following five features: skin involvement, myalgia/muscle tenderness, hypertension, peripheral neuropathy, and renal involvement. Unless a definite diagnosis from imaging or histopathology from tissue biopsy is obtained, diagnosing PAN is challenging. PAN has broad differential diagnosis. Other autoimmune conditions that can mimic PAN include Wegener's granulomatosis, microscopic polyangiitis, giant cell arteritis, and lupus-associated vasculitis. In our case for the above alternatives, p-ANCA, c-ANCA, and anticardiolipin were negative. Furthermore, the above conditions involve the pulmonary artery. PAN usually spares the pulmonary artery. Our case did not have any abnormality of the pulmonary artery. The American College of Rheumatology Classification Criteria for PAN (1990) is a commonly used classification criterion. It includes weight loss >4 kg, livedo reticularis, testicular pain, myalgias, mononeuropathy, diastolic blood pressure >90 mmHg, elevated creatinine 1.5 mg/dl, hepatitis B virus, arteriographic abnormalities, and biopsy of small or medium-sized arteries showing polymorphonuclear cells, so DSA is the preferred mode of imaging of arteries in PAN because magnetic resonance angiography can miss microaneurysms in visceral arteries. Although the present case satisfied 2/10 criteria, there was significant improvement with steroids and cyclophosphamide. Arterial biopsy could not be done due to practical limitations.
The exact mechanism how PAN causes peripheral vascular disease has not been studied yet. It can be due to the associated arterial wall inflammation, endothelial damage, and turbulent blood flow due to arteritis that can give rise to thrombus formation. About 40%–90% of patients demonstrate angiographic findings. The most commonly involved arteries are Mesenteric (33%–36%) and renal (11%–66%). Various therapeutic modalities have been tried in patients with PAN, but a combination of cyclophosphamide and prednisolone has proved most effective. Immunomodulatory agents as well as specific agents targeted against the associated etiological factors are beginning to be tested in the clinical setting. Antiviral therapy in the form of interferon-alpha 2b in combination with plasma exchanges has been tried in PAN related to hepatitis B virus with some degree of success. PAN presenting as peripheral vascular disease with normal visceral artery angiogram and involvement of the lower limb arteries is a rare presentation. Vasculitis-associated neuropathy and other differential diagnosis should be considered. Acute-on-chronic limb ischemia can be caused by thrombosis of inflamed and narrowed arteries.
To conclude, the clinical manifestations and progression of PAN in children are highly variable since it involves multiple systems. Further, PAN presenting as peripheral limb gangrene with arterial thrombus is a very rare presentation.
Since PAN is a seronegative diagnosis, a high index of suspicion should be there for an unexplainable cause of peripheral limb gangrene.
Awareness of autoimmune primary vasculitis presenting as acute limb ischemia, especially in pediatric population, can lead to prompt use of immunosuppression and can save the ischemic limb as anticoagulant drug therapy and vascular surgeries may not be helpful in such cases due to progressive nature of the disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We express our gratitude to Dr. Raju Khubchandani and Dr. Anushka Prabhudesai for helping us in management of this case. We also acknowledge and thank the Dean of our institute, Dr. Ramesh Bharmal, for giving us permission to publish this article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]