|Ahead of print publication
Misdiagnosing sneddon syndrome: Always look skin deep!!
Richa Kumar1, Mylavarapu Harish Kumar2, Abhyam Gupta3, Brijesh Nair1
1 Department of Dermatology, Command Hospital, Kolkata, West Bengal, India
2 Department of Rheumatology, Command Hospital, Kolkata, West Bengal, India
3 Department of Accident and Emergency, Field hospital, Awantipora, Jammu and Kashmir, India
|Date of Submission||09-Jun-2022|
|Date of Acceptance||06-Sep-2022|
|Date of Web Publication||25-Oct-2022|
Department of Dermatology, Command Hospital, Eastern Command, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
We hereby present a case of a 41-year-old female with hypertension and right mastectomy, who presented with bilateral visual loss, weakness of all four limbs, and livedo reticularis of acute onset and was found to have multifocal areas of infarct in bilateral occipital lobes and left external capsule due to antiphospholipid syndrome. Various differentials in the form of sepsis-induced posterior reversible encephalopathy syndrome, posterior circulation stroke, and purpura fulminans confused the final diagnosis of an orphan disease – Sneddon syndrome. This case is reported for the rarity of the disease and the diagnostic dilemmas faced by the nondermatologist in diagnosing this condition even in the presence of striking skin changes.
Keywords: Antiphospholipid syndrome, infarcts, Sneddon syndrome
| Introduction|| |
Sneddon syndrome is an orphan disease characterised by thrombotic vasculopathy, hypertensions and livedo racemose. Patient can present with acute changes such as stroke, vision loss, limb weakness along with the striking skin changes. We report a case of acute onset Sneddon syndrome who had underlying APLA syndrome undiagnosed till before this clinical presentation.
| Case Report|| |
A 41-year-old female presented to the emergency with complaints of weakness of all four limbs, decreased vision, headache, and altered behavior of 1-day duration. The patient was on regular surgical follow-up for a breast abscess which she had developed postmastectomy (right breast), done 15 days ago. There was a history of persistent pus discharge from the site despite multiple courses of antibiotics and dressing.
She also had history of poor oral intake, decreased sleep and restlessness for the past 1 week. There was no history of loss of consciousness. At presentation, she had hypertension (blood pressure [BP]–160/110 mmHg), tachycardia (120/min), and pallor and hypoplastic left-hand digits (history of congenital hypoplastic left upper limb) [Figure 1]. Local examination of the breast shows the postmastectomy status of the right breast with postinfective raw area with healing wound [Figure 2]. She was conscious, Glasgow Coma scale (GCS)-E4V4M6, bilateral plantar– flexor, and DTR-3 + in all limbs. She also had diffuse erythematous to violaceous petechiae and purpure in a lace-like and branched pattern all over the body [Figure 3] and [Figure 4]. Ophthalmic evaluation revealed bilateral decreased vision with PL + in both eyes. She was admitted under emergency medical care and started on antihypertensives and empirical antibiotics with a probable diagnosis of sepsis with purpura fulminans (secondary to postmastectomy breast abscess). On investigations, she had anemia (Hb: 9.9 mg/dl), deranged liver enzymes (alanine transaminase/aspartate aminotransferase/alkaline phosphatase: 89/220/99), and hyponatremia (Na: 126 mEq/ml). Urine routine and microscopy, leukocyte count, platelet counts, coagulation parameters (prothrombin time, INR), complement levels, Anti nuclear antibodies (ANA), procalcitonin, and blood and urine cultures were found to be normal. Electrocardiogram revealed sinus tachycardia and two-dimensional echocardiography was found to be normal. The National Center for Competency Testing of the brain revealed multiple hypointensities (suggestive of subacute infarcts) in the bilateral occipital and left external capsular region [Figure 5]. Magnetic resonance imaging (MRI) of the brain showed multifocal areas of symmetrically altered signals with bilateral occipital involvement suggestive of posterior reversible encephalopathy syndrome (PRES). With no features of sepsis on laboratory workup and normal coagulation profile, the cause of cerebral infarcts and PRES was largely unknown. Further workup revealed raised lupus anticoagulant antibodies (45.70 s), raised beta-2 glycoprotein antibodies (IgA-213.65 SMU, IgM-51.52SMU), anticardiolipin antibodies (52 GPL), and immunoglobulin profile showed decreased IgG and IgM levels. Cryoglobulins, antithrombin III, protein C, and protein S levels were normal. These findings were suggestive of antiphospholipid syndrome (APLA).
|Figure 2: Right mammary region showing postmastectomy status with infected wound over the Operated along with the livedo racemosa lesions|
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|Figure 3: Diffuse erythematous to violaceous petechiae and purpure in a lace-like and branched pattern over B/L lower limbs (Livedo racemosa)|
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|Figure 4: Few lesions over the left lower limb showed superficial ulceration with crusting|
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|Figure 5: NCCT of the brain showing multiple hypointensities (suggestive of subacute infarcts) in bilateral occipital and left external capsular region. NCCT: National Center for Competency Testing|
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Skin changes were identified as livedo racemosa (LR) on review with the dermatologist and skin biopsy confirmed the clinical findings of a medium vessel vasculitis.
In a clinical setting of hypertension, positive radiological changes suggestive of infarcts and PRES, antiphospholipid syndrome with LR, a diagnosis of Sneddon syndrome (SS) was made. The patient was started on anticoagulants and antithrombotic therapy with good response and presently is on follow-up.
| Discussion|| |
SS is a rare noninflammatory thrombotic vasculopathy with an incidence of 4 per 1 million per annum in the general population. It is characterized by the combination of cerebrovascular disease with LR and was described by Sneddon in 1965. Three forms of the syndrome have been described by Schellong et al. Primary, where no causative factor could be identified, autoimmune with antiphospholipid antibodies (aPL) or coexisting systemic lupus erythematosus and a thrombophilic form. Our patient had underlying APLA syndrome which detected during the workup of infarcts. The precise etiology of SS is largely unknown and around 50% of cases are idiopathic, i.e., primary SS. Up to 40%–50% of SS patients are aPL positive where the existence of aPL antibodies suggests that symptoms are secondary to a thrombotic process. Due to the increased risk of a thrombotic or embolic process, smoking and oral contraception have been described as risk factors for developing SS. However, in aPL-negative cases various other abnormalities have been reported and may be encountered in clinical practice, i.e., activated protein C resistance, platelet aggregability, increased thromboglobulin, familial deficiency in antithrombin III, and protein S deficiency.
SS generally occurs in women between the ages of 20 and 42 years. Our patient also fitted into this epidemiological description of SS.
LR has been described as the main characteristic hallmark of SS. It is characterized by dusky erythematous to violaceous, irregular, net-like pattern in the skin. LR may precede the onset of stroke in majority of the cases, seen at presentation with stroke or even later in few cases.,, It is located on the limbs (100% each), trunk (84%–89%), buttocks (68%–74%), face (15%–16%), or hands or feet (53%–59%). Livedo reticularis has been used interchangeably with LR despite their different pathophysiological basis. LR is the appropriate term to be used as per literature as livedo reticularis can be physiological as well.
Stroke is another diagnostic hallmark of SS with the most common clinical signs of hemiparesis, sensory disturbances, aphasia, and visual field disturbances. Headache represents the most frequent unspecific symptom with a higher frequency of headaches in aPL-positive patients as compared to aPL-negative patients. Our patient complained of headache and was incidentally diagnosed to have hypertension when she presented with acute onset of symptoms. Hypertension occurs in a significant proportion (15%–65%) of cases of SS. Patients can develop cognitive impairment and psychiatric disturbances in up to 77% of SS patients which is explained by the multiple recurrent infarcts. Our patient showed cognitive impairment along with altered behavior of acute onset.
Other systemic manifestations in form of heart valvulopathy, decreased renal function, and ophthalmic manifestations due to retinal arterial occlusion have been reported in SS.
Neurological findings can be confirmed on computed tomography (CT) or MRI which can reveal infarcts. In our patient, there were hypodensities on CT, which is a diagnostic feature of SS. The occurrence of PRES has not been specifically mentioned in this disease but it has been described in a clinical setting of hypertension and autoimmune disease, relevant to our patient. Other conditions where PRES has been reported are hypertension associated with kidney injury, sepsis and multiorgan failure, immunosuppressive drugs (tacrolimus, cyclosporine, and chemotherapy), illicit drugs (cocaine), and eclampsia.
The proposed mechanism is the loss of brain autoregulation at rapidly fluctuating BP levels leading to hyperperfusion and cerebral vessel damage., Disordered cerebral autoregulation leads to reactive focal vasoconstriction, thereby resulting in local hypoperfusion, cytotoxic edema, and cerebral infarction.
Based on the presumed pathogenesis of SS, some researchers have recommended long-term anticoagulation and antithrombotic therapy for cerebral ischemic events., Nifedipine has also been tried to reduce skin symptoms but it has not shown improvement in cerebrovascular events.
This case is reported here for the rarity of its occurrence and to highlight the importance of cutaneous examination in a similar complex clinical setup.
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
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]