Abstract
INTRODUCTION: Antisynthetase syndrome (ASS) is triad of myositis, arthritis and interstitial lung disease (ILD) with the presence of anti-aminoacyl-tRNA synthetases. Anti-PL-7 is associated with higher risk of malignancies, particularly solid organ cancers. We present a rare case of ASS in a patient with concomitant diagnosis of peripheral T-cell lymphoma. This uncommon overlap of conditions posed significant diagnostic and therapeutic challenges, highlighting the importance of a multidisciplinary team (MDT) approach for effective management. CASE DESCRIPTION: A 35-year-old Nigerian lady presented in April 2024 with a 6-month history of recurrent chest infections, nights sweats, occasional erythematous rash over wrists and thighs and weight loss. CT thorax revealed bilateral diffuse peribronchial ground glass changes with negative TB-IGRA and ACE. Bronchial washing cultured Staphylococcal Aureus A, which was treated with oral flucloxacillin. In July, she presented with dyspnoea, cough, neck swelling, arthalgia and myalgia. On examination, there were bilateral crackles on auscultation with saturation of 91%, clubbing and multiple tender cervical lymph nodes. Investigations showed CRP:112, TWBC:5.5, ANC:4.1, AEC: 0.1, Hb: 133 and bilateral lung infiltrates on chest X-ray. Ultrasound neck revealed enlarged submandibular, parotid glands with reactive cervical lymph nodes. After 1 week of intravenous flucloxacillin, her condition remained static. Serologic detection of anti-PL7 and anti-Ro-52 suggested a diagnosis of ASS. Rheumatology review unravelled a history of Raynaud’s with proximal weakness worse over lower limbs since March 2024. MMT 8 score was 97/150. There was an enlarged tender submental lymph node with no sicca symptoms and cutaneous features of ASS. CK: 3456, RF: <20, ANA: negative and MRI thighs revealed inflammation over gluteus and quadriceps femoris, confirming myositis. She was pulsed with methylprednisolone 1000 mg, followed with prednisolone 60 mg after cervical lymph node biopsy. She was planned for combination treatment (rituximab, cyclophosphamide and tacrolimus) as per GSTT ILD-MDT. She was briefly started on tacrolimus alone pending fertility preservation attempt but discontinued after peripheral T-cell lymphoma-NOS (CD8+, CD 4-) was confirmed. Extended viral screen was negative, and PET-CT depicted low metabolic lymph nodes in the neck. She was commenced on CHOP under Haematology. The interim PET-CT revealed persistent diffuse inflammatory pulmonary changes. Chemotherapy was withheld and restarted after discussion with GSTT ILD-MDT reiterated anti-PL7 organising pneumonia. Post PET-CT 6 cycles of chemotherapy confirmed remission. She is successfully weaned to prednisolone 10 mg daily. Serial PFT showed improvement with FVC. However, home oxygen may be needed due to desaturation on ambulation. In view of respiratory status, she is ineligible for consolidation autologous stem cell transplant and remains on active surveillance under KCH-Haematology. She remains stable under the care of MDT. DISCUSSION: This case was initially presented with respiratory symptoms, prompting a broad differential diagnosis including infections, sarcoidosis, and ILD. The diagnosis remained unclear until a combination of factors helped narrow the possibilities: poor response to antibiotics, negative ACE and infection screens. The subsequent emergence of myositis, Raynaud’s phenomenon, arthralgia with the detection of anti-PL7 antibodies and anti-Ro 52 ultimately unified a diagnosis of ASS. The diagnostic process was complicated by lymphadenopathy, which later yielded the key histological findings confirming peripheral T-cell lymphoma. The presence of anti-synthetase antibodies and ILD is generally considered to be protective against malignancy; however, our patient uniquely developed lymphoma. Only one case of lymphoma associated with anti-PL7-positive ASS has been reported. It is uncertain if the ASS predated the lymphoma as our patient presented simultaneously with dyspnoea, proximal muscle weakness and lymphadenopathy or whether ASS symptoms helped unmask the underlying pathology which was driving the autoimmune response. The presence of salivary glands enlargement and anti-Ro52 raises a possibility of Sjogren’s syndrome as well. Anti-Ro52 indicative of ILD in association with ASS. This poses question whether there is an autoimmune overlap, bearing in mind the association of Non-Hodgkin’s lymphoma with Sjogren’s; however, this was T cell lymphoma. The coordinated involvement of local respiratory, rheumatology, and haematology teams, alongside specialist input from ILD-GSTT and haematology at KCH was critical in facilitating accurate diagnosis and integrated management which ultimately improved patient outcomes. KEY LEARNING POINTS: This case illustrates the significant diagnostic and therapeutic challenges involved in managing ASS, particularly when it coexists with a hematological malignancy such as peripheral T-cell lymphoma. The patient’s clinical outcome improved through effective collaboration between local and tertiary multidisciplinary teams (MDTs), which was essential given the rarity of this condition and the limitations it placed on treatment options for the autoimmune disease. In our case, myositis and cutaneous manifestations were subtle compared to the ILD, a pattern noted with anti-PL-7 positivity. A comprehensive evaluation, including early rheumatology involvement and antibody screening, may have led to a timely diagnosis. A skin punch biopsy in the initial stages might have aided in the diagnosis and could have perhaps also eliminated cutaneous involvement of T-cell lymphoma Early lymph node biopsy might have expedited the diagnosis and treatment of peripheral T-cell lymphoma, which could potentially have limited the progression of ILD. Nevertheless, the presence of anti-PL-7 and anti-Ro52 antibodies is associated with rapidly progressive ILD. The coexistence of ASS and lymphoma poses complex treatment challenges and underscores the importance of a coordinated, multidisciplinary approach involving rheumatology, haematology, respiratory, and pathology teams. This rare clinical combination highlights the need for a national registry to document malignancies associated with ASS and related antibodies. Such an initiative could promote greater awareness, facilitate earlier recognition, and inform treatment strategies for these difficult cases. In summary, this case emphasises the value of early, comprehensive assessment and the critical role of multidisciplinary collaboration in managing rare and overlapping disease presentations.