Anti‐TIF‐1γ dermatomyositis: Erythematous eruption with weakness and normal creatine kinase

Abstract We describe a case of a previously well 76‐year‐old woman who presented with 9 months of a generalised pruritic rash alongside fatigue, weight‐loss and a symmetrical weakness of the legs.


| CLINICAL FINDINGS
A 76-year-old woman of Afro-Caribbean descent presented with 9 months of a generalised pruritic rash alongside fatigue, weakness and weight-loss.She had a history of septic arthritis and was taking colecalciferol.She had become largely bed-bound, having previously been fully independent.Systems review revealed no other symptoms.
Examination showed widespread erythematous patches with superficial scaling especially affecting the face, chest, abdomen and extensor surfaces of the limbs.They were more severe and sharply demarcated on photo-distributed areas, such as the upper chest and dorsum of the hands (Figure 1).She had generalised non-scarring hair-loss, ragged cuticles and prominent nailfold capillaries.Proximal leg power was 4/5.
Bloods showed slightly raised erythrocyte sedimentation rate (55 mm/hr) and C-reactive protein (41 mg/L).Renal and liver function, creatine kinase (CK) and calcium were normal.An autoantibody screen was positive for anti-transcriptional intermediary factor-1γ (anti-TIF-1γ).Magnetic resonance imaging (MRI) of thighs showed myopathic features.Computerised tomography (CT) and positron emission tomography scans revealed an enlarged subcarinal lymph node with no primary lesion; biopsy of this suggested metastatic adenocarcinoma.
Histopathology showed features of a pauciinflammatory interface dermatitis with compact hyperkeratosis (Figure 2).There was basal cell vacuolar degeneration, patchy pigment incontinence, occasional collections of necrotic keratinocytes and a mild perivascular lymphohistiocytic infiltrate (Figure 2).There was no evidence of a neutrophilic infiltrate or frank vasculitis.Direct immunofluorescence showed globular deposits of IgA and IgM and strong linear positivity of fibrinogen along the basement membrane zone.
It is more common in females (2:1 F:M), with peak incidence in middle age. 2 There is also a juvenile onset form.
Pathogenesis is multifactorial, with autoimmune damage against endomysial capillary endothelium. 1 Both genetic and environmental factors are likely involved.A number of myositis-specific auto-antibodies (MSAs) have been discovered, including anti-Mi-2, anti-MDA-5, anti-NXP-2, anti-SAE and anti-TIF-1.Each MSA subgroup has increasingly understood characteristics, such as an association between anti-MDA-5 and interstitial lung disease (ILD). 2 It is postulated that antibody-associated clinical phenotypes will be incorporated into diagnostic criteria for DM, and will be used increasingly to risk-stratify and manage patients. 2Antibodies to the anti-TIF tumour-suppressor protein subunits (1γ, 1α, 1β) were identified in 2006 and are found in 18%-23% of DM patients. 2Anti-TIF-1γ is more common than anti-TIF-1β, while anti-TIF-1α always coexists with the former. 32][3][4][5] Our patient demonstrates the pruritic rash, Gottrons sign, shawl sign and nail fold changes.Other features of anti-TIF-1 DM include mild myositis, dysphagia and high-risk of malignancy.Associated malignancy has been reported in up to 65% of patients in some studies, although others describe much lower figures. 2An association is particularly seen with anti-TIF-1γ and anti-TIF-1α; risk is also increased in anti-NXP2 DM. 2,3 The most frequently reported malignancies are ovarian, breast, lung, gastric, colorectal and lymphoma. 5n our patient a primary lesion was not found.
Myositis in DM normally involves proximal muscles with symmetrical sub-acute weakness, fatigue and raised CK.Up to 20% of patients have clinicallyamyopathic DM, with no clinical muscle disease. 6This is often mis-diagnosed as subacute lupus erythematous, which also has overlapping histopathological findings. 7Our patient had disabling clinical weakness but a normal CK, complicating diagnosis.Literature describes that CK can be normal in active disease, including in a case report with MDA5 and SAE1 antibodies, and a case series of anti-TIF-1β patients shows normal CK levels with mild muscle weakness. 3,8he most recent diagnostic criteria are the 2017 EULAR criteria, with investigations including muscle enzymes, autoantibodies, skin/muscle biopsy, electromyography and MRI. 9 Screening for malignancy is important, with dermatosis leading to diagnosis in this case.Other investigations may include electrocardiogram and echocardiogram for cardiac involvement, barium swallow for dysphagia, and CT chest and pulmonary function tests for ILD.
Our patient was treated with mometasone 0.1% ointment, tacrolimus 0.1% ointment and 120 mg fexofenadine before receiving 3 doses of pulsed IV methylprednisolone and a weaning regimen of oral prednisolone (from 40 to 10 mg per day).She also underwent radiotherapy.This improved weakness but not the rash.Management is often challenging and many patients require lifelong treatment.Steroid sparing agents can be considered, such as methotrexate or azathioprine.Intravenous immunoglobulin has been used for some patients. 10Management of malignancy is key in malignancy-associated cases, although a case series describes some anti-TIF-1γ patients with a lack of remission despite cure of malignancy. 11Supportive care is important with photoprotection, antipruritics and physical and occupational therapy.
This case illustrates the importance of recognising cutaneous features of DM with normal CK, and the diagnostic delay and disability that can occur.It highlights the severe erythema and malignancy associated with anti-TIF-1γ DM.It is important that patients are not treated as erythrodermic psoriasis with phototherapy, as this worsens DM, and are screened for malignancy.

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I G U R E 1 Panels (a, b) show sharply demarcated extensive erythema on the extensor surface of limbs including the metacarpophalangeal joints of the hand, with photosensitive sparing of the watch strap.F I G U R E 2 (a) Features of a pauciinflammatory interface dermatitis with changes limited to the upper dermis and (b) basal cell vacuolar degeneration with melanin pigment incontinence and scattered necrotic keratinocytes (arrows).4 mm punch biopsy left thigh, haematoxylin and eosin, original magnification (a) 10� and (b) 20�.