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| CASE REPORT |
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| Year : 2019 | Volume
: 17
| Issue : 3 | Page : 80-84 |
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A rare case of digital ischemia and gangrene
Muhammed Jasim Abdul Jalal1, K M Mohammad Iqbal1, Thara Pratap2, Pushpa Mahadevan3
1 Department of Internal Medicine and Rheumatology, Lakeshore Hospital and Research Centre, Kochi, Kerala, India
2 Department of Radiology, Lakeshore Hospital and Research Centre, Kochi, Kerala, India
3 Department of Pathology, Lakeshore Hospital and Research Centre, Kochi, Kerala, India
| Date of Submission | 26-May-2019 |
| Date of Acceptance | 12-Aug-2019 |
| Date of Web Publication | 26-Sep-2019 |
Correspondence Address:
Dr. Muhammed Jasim Abdul Jalal
Department of Internal Medicine and Rheumatology, Lakeshore Hospital and Research Centre, Nettoor P.O., Maradu, NH-47 Byepass, Kochi - 682 040, Kerala
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/cmi.cmi_15_19
Granulomatosis with polyangiitis (GPA) is a small-to-medium vessel vasculitis, which affects multiple organs. We describe a patient with GPA who initially presented with multiple ischemic toes. The diagnosis was supported by a positive c-ANCA (anti-neutrophil cytoplasmic antibody). The involvement of digital arteries in this condition is very unusual, and only a few cases have been reported so far. Keywords: c-ANCA, digital gangrene, granulomatosis with polyangiitis, Wegener's granulomatosis
How to cite this article:
Jalal MJ, Iqbal K M, Pratap T, Mahadevan P. A rare case of digital ischemia and gangrene. Curr Med Issues 2019;17:80-4 |
| Introduction | |  |
Granulomatosis with polyangiitis (GPA) (formerly known as Wegener's granulomatosis, as it was first described by Friedrich Wegener in 1936) is an immunologically mediated small-to-medium vessel vasculitis, which affects multiple organs. It is a type of antineutrophil cytoplasmic antibody (ANCA) vasculitis that is usually associated with c-ANCA.
GPA is diagnosed if there is a minimum of two criteria from the following, as proposed by the American College of Rheumatology (ACR) in 1990:[1]
- Oral ulcers or nasal discharge
- The presence of nodules, fixed infiltrates, or cavities on a chest radiograph
- Abnormal urinary sediment (red blood cell casts or more than five red blood cells per high-power field)
- Granulomatous inflammation on biopsy.
GPA can involve almost any organ system, but the classic organ systems involved include the upper respiratory tract, lower respiratory tract, and kidneys. Ischemia or gangrene of the digital arteries is very rare in this condition. We describe a patient with GPA, who initially presented with multiple gangrenous toes. The diagnosis was supported with a positive c-ANCA (antiproteinase 3 [PR 3]) and kidney biopsy.
| Case Report | | |
A 47-year-old female presented with a history of fever of 3-week duration. She denied chest pain, dyspnea, and palpitation. She gives a history of recurrent episodes of pain in the ear and nostrils. There was a history of intermittent knee joint pains. Our patient had a history of two abortions. While in the hospital, she developed ischemic changes in the right toes, which gradually progressed to blackish discoloration of the toes.
On examination, she was hemodynamically stable with the blood pressure of 110/60 mmHg and heart rate of 84/min. There was no pallor, icterus, cyanosis, clubbing, cervical, or axillary lymphadenopathy. She had bilateral pedal edema. Her right dorsalis pedis and posterior tibial were not felt. The right popliteal artery was poorly felt. All other peripheral pulses were normal. On auscultation, her chest had bilateral rhonchi and crackles. Air entry was bilaterally equal. Heart sounds were regular without any murmurs. The abdomen was soft and nontender. There was no hepatosplenomegaly. Bowel sounds were present. She did not have any femoral/renal bruit. There were no focal neurological deficits.
Her erythrocyte sedimentation rate was 88 and C-reactive protein was positive. Her hepatitis B surface antigen and antihepatitis E virus were all nonreactive. Chest X-ray showed bilaterally fluffy shadows [Figure 1]. Non-contrast computed tomography scan showed multiple scattered nodular non-cavitating pulmonary nodules in the upper lobe ([Figure 2]a and [Figure 2]b, mediastinal window; 2c, lung window). Trucut biopsy was done in the prone position with 18G coaxial needle [Figure 2]d from the left lung lesion and showed linear cores of fibrocollagenous tissue with extensive areas of necrosis [Figure 3]. Granulomas formed of epithelioid histiocytes and giant cells were seen [Figure 4]. Collections of foamy histiocytes with lymphocytes and plasma cells were noted in the stroma. Blood vessels with thrombosis with neutrophils and lymphocytes infiltrating the wall were seen [Figure 5],[Figure 6],[Figure 7]. Special stains for fungus (periodic acid–Schiff and Gomori methenamine silver) and acid-fast bacilli were negative. No malignancy was observed in the biopsy. Positron emission tomography scan demonstrated increased uptake of 18F-fluorodeoxyglucose in the lung nodules. Collaborative evidence from the tru-cut biopsy of the left lung lesion and c-ANCA positivity ruled out lung secondaries. | Figure 1: Chest radiograph of a 48-year-old female patient with proven Wegener's shows ill-defined opacities in both lung fields (a). Repeat radiograph shows complete clearance of lesions after the treatment (b).
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 | Figure 2: Noncontrast computed tomography scan shows multiple scattered nodular noncavitating pulmonary nodules upper lobe, which is the most common finding (a and b, mediastinal window; c, lung window). Tru-cut biopsy was done in the prone position with 18G coaxial needle (d).
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 | Figure 5: Artery with obliterated lumen and leukocytoclastic vasculitis.
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Doppler study of the lower limb showed significant stenosis of the dorsalis pedis and posterior tibial and total occlusion of short saphenous vein.
Taking the overall clinical picture, developing gangrene over the toes, biopsy results from the lung, etc., favored an underlying vasculitis process. GPA and systemic lupus were kept in mind. Antinuclear antibody and dsDNA were negative.
Further evaluation showed c-ANCA positive. p-ANCA and APLA (Antiphospholipid antibody) were negative. 24-h urine protein was 369 mg/day. Coagulation profile (protein C, protein S, and antithrombin III) was within the normal limits.
ECHO showed mild-to-moderate left ventricular dysfunction with an ejection fraction of 40%–45%. Regional wall motion abnormality + coronary angiogram was normal. The peripheral angiogram showed thrombotic occlusion of dorsalis pedis, popliteal artery, and posterior tibial arteries [Figure 8]. Peripheral angioplasty was postponed since the evidence from tru-cut biopsy of the left lung lesion and c-ANCA positivity favored the diagnosis of GPA. | Figure 8: Digital subtraction angiography (a) peripheral angiography of the lower limb shows focal narrowing of popliteal artery (b) with segmental occlusion of posterior tibial and dorsalis pedis artery (c).
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We pulsed her with methyl prednisolone 250 mg intravenous (IV) as infusion daily for 3 consecutive days. Since ANCA-associated vasculitis is resistant to antiplatelet therapy, we considered dual antiplatelets. She was started on dual antiplatelets – ecosprin 75 mg and clopidogrel 75 mg along with anticoagulation (injection Clexane 0.4 mg S/C twice daily).
Recurrent episodes of ear and nose pain, presence of infiltrates in chest radiograph, and tru-cut biopsy of the left lung lesion showing granulomatous inflammation and c-ANCA positivity confirm the diagnosis of GPA in our patient as per the ACR 1990 guidelines.
The choice was between oral/parenteral cyclophosphamide and rituximab infusion. Since oral cyclophosphamide had better results than IV cyclophosphamide, she was started on tablet cyclophosphamide (endoxan 50 mg once daily) along with daily oral septran (cotrimoxazole) as prophylaxis for Pneumocystis jiroveci pneumonia daily. Subsequently, parenteral methylprednisolone was shifted to oral methylprednisolone 16 mg in the morning and 8 mg in the evening.
Later on, she was started on oral anticoagulation with warfarin 5 mg once daily along with injection Clexane, and injection Clexane was subsequently stopped. Her international normalized ratio (INR) was maintained between 1 and 2. Chest X-ray showed complete clearance of fluffy shadows within a week. We discharged her on daily oral cyclophosphamide 50 mg with daily oral cotrimoxazole prophylaxis for P. jiroveci pneumonia with tapering doses of oral methylprednisolone and oral anticoagulation with warfarin. She was asked to come for follow-up every month with complete blood counts, liver and kidney function tests, blood sugars, prothrombin time-INR, and chest X-ray.
| Discussion | | |
GPA presents with cutaneous manifestations in 20% of patients. These include palpable and nonpalpable purpura, papules, subcutaneous nodules, ulcers, digital necrosis, splinter hemorrhages, and vesiculobullous lesions.[1] Digital ischemia as an initial manifestation in GPA is rare and is suspected to be <1%.[1] Destruction of medium-sized vessels and in situ thrombosis due to active vasculitis results in digital ischemia and gangrene.[2] Clinical examination along with angiographic examination supports vasculitic or thrombotic lesions.[3] If not treated, ischemia and gangrene can progress and lead to significant disability. Serology in GPA is positive for anti-neutrophil cytoplasmic autoantibodies (ANCAs) directed against PR 3 or myeloperoxidase. Cyclophosphamide and steroids are the most commonly used treatment capable of inducing remission of active GPA as in alveolar hemorrhage, rapidly progressive glomerulonephritis, central nervous system disease, or other manifestations that are immediately life-threatening.[3] The case reported here responded with steroid and cyclophosphamide therapy.
Our review of literature showed 18 adult GPA patients who presented with digital ischemia and gangrene [3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] [Table 1]. The mean age of patients was 48.3 years and included a range of 24–80 years. Including our patient, 12 of 19 patients were male (63%) compared to 7 of 19 females (37%). Most patients presented with multiorgan involvement, including 14 of 17 with pulmonary involvement (82%), 11 of 17 with kidney disease (65%), and 13 of 17 with sinonasal disease (76%). cANCA was confirmed positive in 13 patients and negative in one patient, and the data were not available in three of the cases. | Table 1: List showing granulomatosis with polyangiitis patients who presented with digital ischemia and gangrene
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Only three patients demonstrated granulomas on biopsy. 10 of 19 cases described isolated involvement of the upper extremities (53%) compared to 5 of 19 with isolated involvement of the lower extremities including our case (26%). Only two cases (11%) have described simultaneous involvement of both the upper and lower extremities.[17] Destruction of medium-sized vessels from active vasculitis explains the pathophysiology of the digital ischemia and gangrene.[17] Active vasculitis resulting in in situ thrombosis can lead to ischemia and gangrene.[17] The diagnosis is usually made based on clinical grounds, but angiographic examination can support vasculitic or thrombotic lesions.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] Pathology can demonstrate either vascular arteritis or thrombi formation.[17] There is no consensus on treatment regarding GPA with digital vasculitis with ischemia and gangrene. However, cyclophosphamide and steroids are the most commonly used treatment in the literature.[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17] Other therapies that have been used include anticoagulation and vasodilators. Surgical intervention with thrombectomy and bypass has been used as well.[10],[11],[12] Digital ischemia and gangrene are rare manifestations of GPA. They can have a heterogeneous presentation as demonstrated by the cases in the literature. Diagnosis can be difficult as biopsy of the skin is often nonspecific. Without treatment, ischemia and gangrene can progress and lead to significant disability. Therefore, it is important for clinicians to be aware of this rare manifestation and institute early treatment as indicated.
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.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1]
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