Rheumatology Advance Access originally published online on December 13, 2005
Rheumatology 2006 45(2):235-237; doi:10.1093/rheumatology/kei074
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LETTER TO THE EDITOR |
Successful treatment of severe Kikuchi's disease with intravenous immunoglobulin
Department of Infection and Tropical Medicine, 1 Department of Cellular Pathology and 2 Department of Radiology, Northwick Park Hospital, Watford Road, Middlesex HA1 3UJ, UK
Correspondence to: M. Noursadeghi. E-mail: mahdad{at}noursadeghi.net
SIR, A 35-yr-old woman presented with a 2-week febrile illness associated with drenching night sweats and progressive swelling in the neck. An excision lymph node biopsy was undertaken (Fig. 1a). This showed reactive hyperplasia with expansion of the paracortex, rich in apoptotic plasmacytoid monocytes (CD123+, CD68+, BCL2–) and phagocytic histiocytes, typical of Kikuchi's lymphadenitis. In view of her protracted symptoms and marked constitutional features, comprising a persistent fever with debilitating malaise, we elected to treat her with prednisolone 40 mg/day. She initially improved, but within 2 weeks had recurrent symptoms. These improved briefly on increasing the prednisolone to 80 mg/day and adding non-steroidal anti-inflammatory drugs, but recurred. Over the subsequent 2–4 weeks she developed progressive cushingoid changes and the steroid dose was gradually reduced. Her lymph nodes continued to enlarge (Fig. 1b), culminating in an emergency admission when she presented with signs of impending airway obstruction, dysphagia to solids and periorbital oedema. Because of the unusual clinical progression, a further lymph node biopsy was performed and confirmed the diagnosis. There was no sustained therapeutic response to either 1 g intravenous methylprednisolone daily for 3 days or a trial of thalidomide 200 mg/day for 7 days.
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The severity of her head and neck swelling made us consider other empirical anti-inflammatory therapies. Intravenous immunoglobulin (IVIG) was chosen because, compared with cyclophosphamide, anti-tumour necrosis factor (TNF) antibodies (e.g. infliximab) or soluble TNF receptor (etanercept), it incurred least risk of adverse effects. We administered IVIG at 0.4 g/kg per day for 3 days. A definite improvement in her facial swelling occurred within 4 days, followed by gradual but complete resolution of lymphadenopathy over the subsequent 8 weeks, despite stopping steroid medication altogether. Her lymphadenopathy resolved completely by 8 weeks and she remained well during 8 months of follow-up.
Kikuchi's disease is an idiopathic illness characterized by a self-limiting lymphadenitis that normally resolves over subsequent weeks or months without specific treatment [1]. A handful of fatal cases have been described in addition to sparse reports of empirical treatment with a diverse selection of agents, which include antimicrobial and anti-inflammatory drugs [1–4]. Although associations with infective agents have been reported, a causal link has not been established. Instead, several lines of evidence support an association with systemic lupus erythematosus (SLE). This may precede, coincide with or develop after the presentation of Kikuchi's disease [5, 6]. Lymph node expansion in Kikuchi's disease is principally due to apoptotic CD123+ plasmacytoid monocytes [1, 7], which are also recruited to cutaneous lesions in SLE and may be the source of high IFN-
levels in active disease [7]. Furthermore, accumulation of apoptotic plasmacytoid monocytes in Kikuchi's disease shows parallels with defective clearance of apoptotic cells in SLE [8] and supports a pathogenetic association. Tender lymphadenitis and fever in Kikuchi's disease may cause significant morbidity and has led to a range of empirical treatments. Apparent therapeutic responses to minocycline [2] and ciprofloxacin [3] have been used as supportive evidence for an infective aetiology in Kikuchi's disease, but in each case the time course of recovery was consistent with the natural history in most patients. A similar observation has been made for hydroxychloroquine [4] and used to support the association with SLE. The most frequent reports are of treatment with corticosteroids, to which most patients seem to respond, even with relatively short courses or low doses [1]. Despite transient remission of symptoms when we treated our patient with prednisolone, her prompt relapse was subsequently resistant to further corticosteroids, even at very high doses. By the time she presented with thoracic outlet obstruction due to lymphadenopathy, her illness had lasted longer than expected, with no signs of resolution. Her subsequent recovery within days of starting the course of IVIG was therefore striking.
The specific therapeutic effect of IVIG in a patient presenting solely with Kikuchi's disease has not been described before. Interestingly, however, two case reports describe a therapeutic response to combined treatment with IVIG and corticosteroids in children with haemophagocytic syndrome and concurrent Kikuchi's lymphadenitis [9, 10], providing additional support for our observation. IVIG has become established in the treatment immunological and inflammatory diseases, including SLE, by virtue of diverse immunomodulatory mechanisms [11]. Anti-idiotype antibodies against autoantibodies and competition with endogenous autoantibodies for binding of Fc
receptors or complement components may be important in autoimmune diseases. Its interaction with complement, which normally provides potent amplification of inflammatory responses, may underlie the observation that IVIG has more non-specific anti-inflammatory effects, and may be effective in conditions where no autoantibody has been demonstrated. Modulation of T-cell-dependent inflammation is also described, although the mechanism is not clear. In view of its pluripotent effects, IVIG therefore represents a suitable candidate for empirical treatment of idiopathic inflammatory conditions such as Kikuchi's disease, which may ultimately represent common downstream effects of dysregulated immunological responses with heterogeneous aetiologies.
We are indebted to Professor Tiny Maini for helpful clinical discussion of this case.
The authors have declared no conflicts of interest.
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