Diabetic myonecrosis: an unusual mimicker of idiopathic inflammatory myositis

15 Aug 2021 Ayurveda, Cardiac, Lifestyle

Introduction

Diabetic myonecrosis or diabetic muscle infarction, was first described by Angervall and Stener in 1965. It is a very rare, under-recognised complication of poorly controlled long-standing diabetes mellitus with associated complications like nephropathy, retinopathy and neuropathy. Fewer than 200 cases have been reported in literature.

Case presentation

A 59-year-old male, with poorly controlled type 2 diabetes mellitus (T2DM) for the last ten years, and hypertension for five years, presented with three months’ history of insidious onset bilateral thigh pains. Intensity of pain gradually increased, making the patient bed-bound for ten days prior to presentation. He also had diabetic nephropathy for the previous year, bilateral diabetic retinopathy for four months, and diabetic mononeuropathy of the left ulnar nerve for one month. He had a history of similar pain in his right thigh three years before, which had improved gradually over two months with low-dose oral steroids and analgesics received elsewhere.

Examination revealed mild swelling all over both thighs, with overlying cutaneous erythema and tenderness of the thigh muscles. Muscle power at the hips and knees could not be assessed due to pain; however, it was normal at the lower legs, upper limbs and neck. The possibility of idiopathic inflammatory myositis (IIM) was considered in view of symmetrical myalgia and muscle tenderness of the proximal groups of lower limbs.

On evaluation, deep vein thrombosis (DVT) was ruled out. Creatine phosphokinase (CPK) was 354 IU/l (normal range is 20–200IU/l). MRI of the thighs, performed during a previous episode in 2015, showed increased bulk of the right vastus lateralis muscle with hyperintense signal on short tau inversion recovery (STIR) images (arrow in Figure 1a,1b) and hypointense signal on T1-weighted images. MRI of the thighs during the present episode demonstrated similar changes, but this time with symmetrical involvement of multiple muscle groups (hip adductors, abductors, quadriceps and hamstrings) (arrows in Figure 1c). Review of histopathology slides of muscle biopsy from the right vastus lateralis performed in 2015 (Figure 2), showed ischaemic necrosis of muscle fibres (arrows) with scattered lymphocytes (arrowheads). Antinuclear antibody and anticardiolipin antibodies were negative. Other laboratory data are summarised in Table 1. CPK during the previous episode was 308IU/l, with a normal range of 39–300IU/l.

Figure 1a MRI of the right thigh in 2015 showing increased bulk of the right vastus lateralis muscle with hyperintense signal on STIR image (arrow) in coronal plane

Figure 1b MRI of the thighs in 2015 showing increased bulk of the right vastus lateralis muscle with hyperintense signal on STIR image (arrow) in transverse plane

Figure 1c MRI of the thighs during present episode, showing increased bulk of the bilateral multiple muscles with hyperintense signal on STIR image (arrows) in coronal plane

Table 1 Laboratory data

White blood cell count (4000–11000 /mm3) 9700
Erythrocyte sedimentation rate (0–20 mm/hr) 63
Aspartate aminotransferase (7–40 IU/l) 27
Creatine phosphokinase (20–200 IU/l) 354
Lactate dehydrogenase (200–400 IU/l) 235
Serum creatinine (0.9–1.4 mg/dl) 3.0
Haemoglobin A1C (4–6 %) 8.6
24 hour urine proteins (< 0.15 grams/day) 3.7

Taking into consideration the following points: long-standing poorly controlled diabetes, concomitant presence of other microvascular complications of diabetes, past history of similar myalgia in the right thigh with myonecrosis on muscle histopathology, normal muscle power at the upper limbs and neck, absence of cutaneous and other manifestations of IIM, CPK being just above the normal upper limit, the absence of antinuclear antibodies and the poor general condition of the patient, muscle biopsy was deferred and a diagnosis of recurrent DMI was made. The hypertension was treated appropriately, blood glucose was controlled with insulin and bed rest was advised with DVT-prophylaxis measures. The patient also received opioid analgesics and aspirin. He had minimal pain relief during his hospital stay, but over the next two months the pain gradually decreased and he was able to ambulate with support. This clinical improvement without the use of any immunosuppressant strongly supported the diagnosis of DMI.

Figure 2 Histopathology of muscle biopsy from the right vastus lateralis in 2015 showing ischaemic necrosis of muscle fibres (arrows) with scattered lymphocytes (arrowheads)

Discussion

DMI is a rare complication of DM. It presents with acute onset of spontaneous muscular pain and swelling, most commonly unilaterally in the thighs.2

A systematic review of DMI found 126 cases reported in the literature over 48 years, of which 54% were females. Half of the patients had T2DM, with a mean age of 52.2 years, whereas the mean age in patients with type 1 diabetes mellitus (T1DM) was 35.9 years. The mean duration of T2DM at the time of DMI diagnosis was 11 years, and for T1DM it was 18.9 years. Concurrent retinopathy, nephropathy and neuropathy was seen in 46.6% of patients. The mean HBA1c value at the time of DMI diagnosis was 9.34%. Nephropathy, which is the most common microvascular complication of DM, was seen in 75% of cases.2 Bilateral involvement is seen in 8% to 33% of cases.3,4 The most frequently affected muscles reported are the vastus medialis and vastus lateralis, though many other muscles can be affected.2,4 Laboratory investigations for DMI are relatively non-specific.3 CPK may be normal or increased.

The pathogenesis of DMI is unknown. Thromboembolic events secondary to microvascular endothelial damage may cause tissue ischaemia and trigger an inflammatory response. Generation of free radicals due to reperfusion injury, and increased pressure within the fascial compartment due to tissue oedema, may lead to local hypoxia culminating in infarction. The presence of hypercoagulable state in diabetes, due to alteration of coagulation-fibrinolysis system, with increased levels of factor VII, fibrinogen, thrombomodulin, and decreased levels of antithrombin and tissue plasminogen activator may also contribute.2,3,4,5

Idiopathic inflammatory myositis was considered due to presentation in bilateral thighs. The classic unilateral presentation of DMI may be confused with DVT, pyomyositis, cellulitis, necrotising fasciitis or malignancy.6 Though weakness is the most prominent symptom in IIM, sometimes myalgia may be the only presentation.7,8 MRI is the imaging modality of choice in either condition, but does not differentiate these two conditions. In both the affected muscles show hyperintensities on T2-weighted and STIR images, and hypointensities on T1-weighted images, with associated perifascial, perimuscular and/or subcutaneous oedema.9 Muscle biopsy can provide a definitive diagnosis in such cases. The tissue is pale and large areas of muscle fibre necrosis are seen under the microscope. If the diagnosis is certain on the basis of non-invasive investigations, muscle biopsy is not recommended, since mean time to symptom resolution may be increased in patients undergoing this procedure.2

DMI resolves spontaneously over a few weeks to months in most patients.5 Management is mainly supportive, consisting of aspirin, analgesics, bed rest and controlling blood glucose levels. Onyenemezu and Capitle compared surgery, physiotherapy and bed rest in the treatment of DMI and found that the patients undergoing surgery (muscle excision biopsy ) had significantly prolonged symptom recovery time when compared to those managed by physiotherapy or bed rest.10 Horton et al. also showed that time to recovery was numerically lower in patients who received supportive care (glycaemic control and pain management/best rest) plus a nonsteroidal anti-inflammatory drug, than those who were managed only by bed rest.2 The recurrence rate of DMI is found to be lowest with bed rest followed by physiotherapy and was highest in those who underwent surgery.10

Patients with DMI are at high risk of recurrence, which is reported to be from 34.9% to 45.0% in different studies, and in about two-thirds of patients these recurrences are noted in a different location or muscle group than in the initial presentation.2,3 Our patient had recurrence of DMI after three years with current involvement of multiple muscle groups.

Table 2 Pointers for suspecting DMI

Long-standing poorly controlled DM with presence of other microvascular complications
Acute onset focal or multifocal myalgia without fever and trauma
Tenderness of involved muscle with or without overlying cutaneous erythema
T2/STIR hyperintensities with muscle oedema of one or more muscles on MRI

Though DMI is very rare, physicians who manage DM should be aware of this complication and should suspect it in the presence of the pointers listed in Table 2. In clinically suspected cases MRI helps in reaching a diagnosis, and in atypical cases muscle biopsy may help further by demonstrating muscle infarction.

Conclusion

The present case is of interest as the patient had recurrent DMI, a rare complication of T2DM, presenting with bilateral thigh myalgia which showed bilaterally symmetrical hyperintensities of multiple muscles on MRI. Increased awareness regarding this entity among physicians may help in timely diagnosis and in avoiding a battery of unnecessary investigations.

References

1 Angervall I, Sterner B. Tumoridorm focal muscular degeneration in two diabetic patients. Diabetologia 1965; 1: 39–42.

2 Horton WB, Taylor JS, Ragland TJ et al. Diabetic muscle infarction: a systematic review. BMJ Open Diabetes Res Care 2015; 3:e000082.

3 Kapur S, Brunet JA, McKendry RJ. Diabetic muscle infarction: case report and review. J Rheumatol 2004; 31: 190–4.

4 Trujilo-Santos AJ. Diabetic muscle infarction: an underdiagnosed complication of long standing diabetes. Diabetes care 2003; 26: 211–5.

5 Bhat T, Naik M, Mir MF et al. Recurrent diabetic muscle infarction, a rare complication of diabetes: a case report. Egypt Rheumatol Rehabil 2017; 44: 181–4.

6 Rastogi A, Bhadada SK, Saikia UN et al. Recurrent diabetic myonecrosis: a rare complication of a common disease. Indian J Med Sci 2011; 65: 311–5.

7 Ahmed HN, Chhaya SK, Makdissi A et al. Diabetic muscle infarction: case report of a rare complication. Am J Med 2007; 120: e3-e5.

8 Ascherman DP, Aggarwal R, Oddis CV. Classification, epidemiology, and clinical features of inflammatory muscle disease. In: Marc C, editor. Hochberg, 7th ed., Vol.2. Philadelphia: ElsevierInc.; 2019; pp. 1293–305.

9 Gupta S, Goyal P, Sharma P et al. Recurrent diabetic myonecrosis – an under-diagnosed cause of acute painful swollen limb in long standing diabetics. Ann Med Surg (Lond) 2018; 35: 141–5.

10 Onyenemezu I, Capitle E Jr. Retrospective analysis of treatment modalities in diabetic muscle infarction. Open Access Rheumatol Res Rev 2014; 6: 1–6.

Reactive arthritis after SARS-CoV-2 infection

18 Jul 2021 Ayurveda, Lifestyle, Rehabilitation

DEAR EDITOR, ReA, a subtype of SpA, is a sterile inflammatory arthritis, predominantly involving the lower extremities. It usually occurs 1–3 weeks after a remote mucosal infection (gastrointestinal or genitourinary). It is also known as Reiter’s syndrome in the presence of the classical triad: urethritis in men and cervicitis in women, ocular inflammation (conjunctivitis or uveitis) and arthritis of large joints. Chlamydia trachomatis, Campylobacter, Salmonella, Shigella and Yersinia are a few of the common bacterial infections that can cause ReA [1]. A few other bacteria and viruses have also been associated with the pathogenesis of ReA. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as a cause of ReA has been reported previously in six cases [2–7]. Here, we report a case of ReA after SARS-CoV-2 infection. Written informed consent was obtained from the patient.

A 27-year-old female was hospitalized after 2 days of fever and body aches. On evaluation, SARS-CoV-2 RT-PCR from a nasopharyngeal swab was positive, and CT imaging of the chest showed bilateral peripheral ground glass opacities COVID-19 Reporting and Data System (CO-RADS-4). Other laboratory parameters during hospitalization showed leucopenia (3200/mm3), elevated CRP (114 mg/l) and D-dimer (three times upper normal limit), and normal levels of lactate dehydrogenase, ferritin and IL-6. She was diagnosed with coronavirus disease 2019 (COVID-19) pneumonia and received 1 mg/kg CS in the form of oral methylprednisolone and favipiravir. Oxygen saturation was well maintained on room air throughout the disease course. Fever subsided on day 3 of hospitalization, and she was discharged on day 8 with tapering doses of CS. Two weeks after testing positive for SARS-CoV-2 infection, while on 0.25 mg/kg of CS, she developed acute onset arthritis in both lower extremities and relatively mild arthritis in the small joints of the right hand. She did not have any history of recent diarrhoea, cervicitis or uveitis.

On examination, bilateral knee, ankle and midfoot joints were extremely tender and swollen. Mild tenderness was also noted in the small joints of the right hand (wrist, MCP and PIP joints). The rest of the physical examination was normal. RT-PCR for SARS-CoV-2 was negative. RF was positive in low titres. ACPA, ANA and HLA-B27 were negative. A probable diagnosis of ReA secondary to SARS-CoV-2 infection was made. She received NSAID and additionally required oral opioid analgesic to manage the pain. CS was gradually tapered and stopped over next 3 weeks. At 4-week follow-up, the arthritis had improved significantly, allowing withdrawal of opioid analgesic and tapering of NSAID.

Although ReA causes asymmetric oligoarthritis in the lower extremities, a mild form of upper limb arthritis can also occur, as seen in our patient [6]. In contrast to this, Danssaert et al. [5] reported arthritis of unilateral hand joints without involvement of lower extremities. Liew et al. [4] described a patient with acute right knee arthritis manifesting 3 days after fever and simultaneously being positive for SARS-CoV-2 infection. Schenker et al. [6] and De Stefano et al. [7] described cases of ReA associated with cutaneous vasculitis and psoriatic skin lesions, respectively. The patient reported by Ono et al. [2] had severe respiratory distress requiring mechanical ventilation, whereas respiratory involvement was milder in the other five patients [3–7], including our patient. All these cases are summarized in Table 1.

Table 1

Reported cases of possible reactive arthritis after SARS-CoV-2 infection

Parameter Ono et al. [2] Saricaoglu et al. [3] Liew et al. [4] Danssaert et al. [5] Schenker et al. [6] De Stefano et al. [7] Our case
Age, years 50 73 47 37 65 30 27
Sex Male Male Male Female Female NA Female
Onset of ReA after SARS-CoV-2 infection, days 22 14 Simultaneous 12 ˃10 20 14
Musculoskeletal manifestations Ankles, right Achillis enthesitis Hands, feet Knee Hand Knees, ankles, wrists Right elbow Knees, ankles, feet, hand
Other manifestations – – Balanitis – Cutaneous vasculitis Psoriatic skin lesions –
RF − − NA − − − +
ACPA − − NA NA − − −
HLA-B27 − NA NA NA + − −
ANA − NA NA + − − −
Arthrocentesis No crystals, sterile NA No crystals, sterile NA NA No crystals Not done
Radiograph Normal Normal Normal NA NA NA Not done
Treatment NSAID, IA CS NSAID NSAID, IA CS Opioid, gabapentin CS NSAID, topical CS for skin NSAID, opioid
Parameter Ono et al. [2] Saricaoglu et al. [3] Liew et al. [4] Danssaert et al. [5] Schenker et al. [6] De Stefano et al. [7] Our case
Age, years 50 73 47 37 65 30 27
Sex Male Male Male Female Female NA Female
Onset of ReA after SARS-CoV-2 infection, days 22 14 Simultaneous 12 ˃10 20 14
Musculoskeletal manifestations Ankles, right Achillis enthesitis Hands, feet Knee Hand Knees, ankles, wrists Right elbow Knees, ankles, feet, hand
Other manifestations – – Balanitis – Cutaneous vasculitis Psoriatic skin lesions –
RF − − NA − − − +
ACPA − − NA NA − − −
HLA-B27 − NA NA NA + − −
ANA − NA NA + − − −
Arthrocentesis No crystals, sterile NA No crystals, sterile NA NA No crystals Not done
Radiograph Normal Normal Normal NA NA NA Not done
Treatment NSAID, IA CS NSAID NSAID, IA CS Opioid, gabapentin CS NSAID, topical CS for skin NSAID, opioid

NA: not available.

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Table 1

Reported cases of possible reactive arthritis after SARS-CoV-2 infection

Parameter Ono et al. [2] Saricaoglu et al. [3] Liew et al. [4] Danssaert et al. [5] Schenker et al. [6] De Stefano et al. [7] Our case
Age, years 50 73 47 37 65 30 27
Sex Male Male Male Female Female NA Female
Onset of ReA after SARS-CoV-2 infection, days 22 14 Simultaneous 12 ˃10 20 14
Musculoskeletal manifestations Ankles, right Achillis enthesitis Hands, feet Knee Hand Knees, ankles, wrists Right elbow Knees, ankles, feet, hand
Other manifestations – – Balanitis – Cutaneous vasculitis Psoriatic skin lesions –
RF − − NA − − − +
ACPA − − NA NA − − −
HLA-B27 − NA NA NA + − −
ANA − NA NA + − − −
Arthrocentesis No crystals, sterile NA No crystals, sterile NA NA No crystals Not done
Radiograph Normal Normal Normal NA NA NA Not done
Treatment NSAID, IA CS NSAID NSAID, IA CS Opioid, gabapentin CS NSAID, topical CS for skin NSAID, opioid
Parameter Ono et al. [2] Saricaoglu et al. [3] Liew et al. [4] Danssaert et al. [5] Schenker et al. [6] De Stefano et al. [7] Our case
Age, years 50 73 47 37 65 30 27
Sex Male Male Male Female Female NA Female
Onset of ReA after SARS-CoV-2 infection, days 22 14 Simultaneous 12 ˃10 20 14
Musculoskeletal manifestations Ankles, right Achillis enthesitis Hands, feet Knee Hand Knees, ankles, wrists Right elbow Knees, ankles, feet, hand
Other manifestations – – Balanitis – Cutaneous vasculitis Psoriatic skin lesions –
RF − − NA − − − +
ACPA − − NA NA − − −
HLA-B27 − NA NA NA + − −
ANA − NA NA + − − −
Arthrocentesis No crystals, sterile NA No crystals, sterile NA NA No crystals Not done
Radiograph Normal Normal Normal NA NA NA Not done
Treatment NSAID, IA CS NSAID NSAID, IA CS Opioid, gabapentin CS NSAID, topical CS for skin NSAID, opioid

NA: not available.

Other manifestations of ReA include inflammatory back pain, dactylitis, enthesitis, tendinitis and bursitis. There are no specific laboratory tests for ReA, and diagnosis relies on the typical clinical presentation with detection of the triggering infection [8]. Arthritis persists for >6 months in 30–50% of patients [1]. The most effective treatment for ReA is NSAID. IA glucocorticoid can be used for mono- or oligoarticular disease. In chronic cases, SSZ can be effective when started within 3 months of disease onset [8].

Our patient developed lower limb predominant inflammatory arthritis, 2 weeks after SARS-CoV-2 infection. The presence of RF in low titres was possibly attributable to an immune response to the recent infection. The classical clinical picture, a preceding infection, absence of other autoantibodies, absence of autoimmunity in the family and response to NSAID, supported the diagnosis of ReA.

This case, along with previously reported cases, suggest SARS-CoV-2 infection as an aetiology in the pathogenesis of ReA. More observations are required to strengthen this association.

Key message

• ReA should be considered in patients with acute arthritis after SARS-CoV-2 infection.

Funding: No specific funding was received from any funding bodies in the public, commercial or not for-profit sectors to carry out the work described in this manuscript.

Disclosure statement: The authors have declared no conflicts of interest.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Recurrent scleritis as a presenting manifestation of asymptomatic occult Takayasu arteritis

18 Jun 2021 Cardiac, Lifestyle

DEAREDITOR, Takayasu arteritis is a rare chronic granulomatous large-vessel vasculitis with preferential involvement of the aorta, its major branches and the pulmonary arteries [1]. Ocular involvement in Takayasu arteritis is seen as Takayasu retinopathy, which is the result of ocular hypoperfusion and chronic ischaemia [2]. Scleritis in Takayasu arteritis is extremely rare, reported in only six cases [3–6]. We report a case of previously undiagnosed asymptomatic Takayasu arteritis presenting with bilateral recurrent anterior scleritis.

A 48-year-old woman presented with redness and pain in the right eye for 15 days. Pain radiated around the eye and was exacerbated by eye movements. She had history of multiple episodes of inflamed, painful eyes for past 6 years, involving the left eye for the initial 4 years and the right eye thereafter. She received topical CSs and NSAIDs, and oral CSs at variable doses during these episodes.

Examination of the eyes showed temporal congestion in the right eye (Fig. 1A) and a normal left eye. Ophthalmic assessment confirmed nodular anterior scleritis of the right eye. Visual acuity, the cornea, anterior and posterior chambers were normal in both eyes. Further physical examination revealed absent pulses in the left radial, ulnar, brachial and subclavian arteries. Right radial and brachial pulses were diminished. Bruits were heard over bilateral carotid and left subclavian arteries. Blood pressure was not recordable in the left arm, 90/60 mmHg in the right arm and 130/80 mmHg in both lower limbs.

Fig. 1

Scleritis in Takayasu arteritis

(A) Anterior scleritis. (B) CT angiogram, showing circumferential wall thickening in ascending (arrow) and descending thoracic aorta (arrowhead). (C) CT angiogram, showing stenosis in right common carotid and bilateral subclavian arteries (arrowheads), with complete occlusion in proximal part of left subclavian artery (arrow).

On evaluation, ESR was 49 mm/h, CRP was 20.4 mg/l, and ANCAs (ELISA and immunofluorescence) and ANA tests were negative. Chest radiographs and echocardiographs were normal. CT angiogram showed circumferential wall thickening in the ascending (arrow in Fig. 1B), arch and descending thoracic aorta (arrowhead in Fig. 1B) and the brachiocephalic, left common carotid and left subclavian arteries. Complete occlusion was seen in the proximal part of the left subclavian artery (arrow in Fig. 1C), with collaterals filling the distal segment. Stenosis was seen in the right common carotid and bilateral subclavian arteries (arrowheads in Fig. 1C). A diagnosis of Takayasu arteritis with anterior nodular scleritis was made, and oral prednisolone was started at 1 mg/kg in combination with oral MTX 15 mg/week. Ocular symptoms improved markedly over the next few days, and gradual tapering of prednisolone dose was planned.

We have found only six published cases of Takayasu arteritis associated with scleritis [3–8]. Akhtar et al. [3] reported a case with a 10-year history of Takayasu arteritis. The patient was in prolonged remission before developing scleritis as a presenting manifestation of disease flare. Scleritis was refractory to MMF and required adalimumab for CS weaning. Scleritis as a presenting manifestation in an asymptomatic occult Takayasu arteritis was reported only once [7]. This patient succumbed to ischaemic colitis 3 weeks after presentation, and necrotizing granulomatous vasculitis of the thoracic and abdominal aorta was demonstrated on autopsy. Similar to our case, Chaudhary et al. [8] also reported a case of Takayasu arteritis with a 6-year-long history of fluctuating scleritis. But unlike their patient, our patient was asymptomatic for Takayasu arteritis and had occult vascular inflammation for an unknown duration, leading to stenosis and occlusion of vessels. This presentation makes our case extremely unusual and also emphasizes the importance of detailed physical examination even in patients presenting with isolated scleritis.

Small vessel vasculitis in Takayasu arteritis is less well described. Different cutaneous manifestations with histopathological evidence of vasculitis have been reported in Takayasu arteritis [9]. Scleritis in our patient could also be a small vessel manifestation of Takayasu arteritis. However, the possibility of these two conditions coexisting cannot be excluded.

Key message

  • Takayasu arteritis should be in the list of differential diagnoses in patients with isolated scleritis.

Funding: No specific funding was received from any funding bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

Disclosure statement: The authors have declared no conflicts of interest.

Data availability statement

Data are available upon reasonable request by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). All data relevant to the study are included in the article.

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