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Neuro-Sweet disease: A diagnostic challenge
Journal of the Neurological Sciences 371 (2016) 42–44
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Neuro-Sweet disease: A diagnostic challenge Keywords: Neuro-Sweet disease Migraine Magnetic resonance imaging
1. Introduction Sweet disease (SD), also known as acute febrile neutrophilic dermatosis, is an inflammatory dermatologic disease, characterized by malaise, fever, leukocytosis and cutaneous edematous erythematous plaques that heal without scarring [1]. Skin biopsy of lesions reveal deep dermal infiltration of mature neutrophils and the absence of vasculitis [2]. The etiopathogenesis is unknown; however an association with HLA-B54 and HLA-Cw1 has been reported [3]. SD with central nervous system involvement has been reported as Neuro-Sweet disease (NSD) [4]. The most common neurological manifestation is encephalitis and meningitis, but headache, consciousness disturbance, epilepsy, involuntary movements, parkinsonism, paresthesias, hemiparesis or tetraparesis have been reported [4–6]. Cerebrospinal fluid examination (CSF) might show a mild increase in protein and mild pleocytosis, with a predominance of lymphocytes. Brain magnetic resonance imaging (MRI) could demonstrate abnormal alterations mainly in basal ganglia, thalamus, brainstem and less frequently in subcortical white matter [4,7]. Systemic corticosteroid therapy is highly effective for the treatment of NSD, otherwise other drugs (potassium-iodide, colchicine, dapsone, indomethacin and ciclosporin) could be used as a second option [1]. Usually, NSD is benign with rare neurological sequelae, however, there is a high frequency of symptom relapse, with persistent lesions on brain MRI [4]. The diagnosis of NSD is not easily achieved; often a misdiagnosis of other systemic autoimmune disease is made. We report the case of an Italian woman with SD, early atypical neurological involvement, multiple cortical-subcortical lesions in brain MRI and negative HLA-B54/Cw1.
2. Case report A 52-year-old woman, with migraine since her adolescence, presented with painful erythematous vesicles, weakness, fever and arthralgia. These symptoms were preceded by a respiratory infection. Skin lesions were detected asymmetrically on the upper trunk and limbs. Laboratory tests showed no abnormalities. Skin biopsy revealed acute neutrophilic dermatoses and allowed a Sweet disease diagnose. She
http://dx.doi.org/10.1016/j.jns.2016.10.012 0022-510X/© 2016 Published by Elsevier B.V.
was treated with Metylprednisolone 40 mg/die for seven days, then tapered, and her symptoms disappeared. Five months after the onset of Sweet disease the patient came to our attention complaining weakness, left hemisoma hyposthenia and headache, described unusual and non-responder to common drugs. Her neurological examination showed a mild impairment of the left pyramidal tract. No skin lesions were detected. A brain MRI revealed multiple hyperintense lesions in the corticalsubcortical junction in frontal and temporal regions bilaterally, without Gadolinium enhancement or diffusion restriction (Fig. 1A–B). Her cervical MRI did not present abnormalities. CSF showed a mild increase in protein and 2 lymphocytes. Oligoclonal bands were detected with a type 4 pattern, indicating systemic inflammation. Typing for HLA resulted negative for HLA-B51/B54/Cw1, but positive for HLA-B07/B49/C07. No abnormalities in routine nerve conduction studies were found. Tumor marker tests revealed no evidence of malignancy. She was retreated with corticosteroid therapy (Prednisone 60 mg die for 6 weeks) and recovered. Considering her history, symptoms, the MRI and CFS findings and her good response to steroid therapy, according to published criteria [4], the diagnosis of probable Neuro-Sweet disease was made. When the steroid therapy was gradually tapered, the patient complained relapse of the usual symptoms. At 7-month follow-up the patient had relapse of migraine and her MRI showed a new hyperintense lesion in the left frontal semioval center and confirmed the previously described lesions, all without Gadolinium enhancement or diffusion restriction (Fig. 1C–D). At 2-year follow-up the patient had a new relapse of migraine episodes and arthralgia, MRI was unchanged and CFS still showed mild increase in protein. We explained to the patient that preventive therapy for relapse remains to be established. We have, therefore, decided to treat migraine with specific therapy (Topiramate 25 mg die) and possibly use corticosteroid therapy only for relapses. The patient responded well.
3. Discussion The patient presented clinical features of cutaneous manifestation of SD but sub-sequentially showed an atypical neurological involvement, suggesting a systemic autoimmune disease. There is frequent overlap between NSD and other autoimmune diseases (Multiple sclerosis, Beҫhet disease, Systemic Lupus Erythematous, Chron's disease) and it could be also associated to malignancies and drug exposure [1,8]. In this case we ruled out these conditions. In particular, we excluded a demyelinating disease because this diagnose was not supported by MRI and CFS findings. Beҫhet disease was excluded because of the absence of cutaneous vasculitis, thrombosis in skin biopsy and the negative HLA-B51 typing.
Letter to the Editor
43
Fig. 1. (A–B) Hyperintense lesions in white matter, cortical-subcortical junction. FLAIR. ADC. (C–D) 7 month follow-up: new hyperintense lesion in frontal left white matter. FLAIR.
We considered the diagnosis of probable NSD on the basis of skin lesions with neutrophilic infiltrate, the detection of albumin-cytologic dissociation on CFS with oligoclonal bands positive for type 4 (characteristic of systemic inflammation), multiple hyperintense lesions in the cortical-subcortical regions and the clinical improvement after low dosage oral steroid therapy. The diagnosis requested some weeks and was attended by different specialists, in particular the Dermatologist and Neuroradiologist. Although our patient fulfilled most of the diagnostic criteria for NSD [4], her case seems atypical, due to: – onset and manifestations: in most case reports [4] the clinical onset is an aseptic meningo-encephalitis associated to cutaneous manifestations. Our patient complained migraine and pyramidal syndrome after the SD diagnosis, which is reported in 44,9% of cases [10]; – MRI: typical lesion sites in NSD are in basal ganglia, thalamus and brainstem [4], in this case lesions were detected in frontal and temporal regions bilaterally; – race: NSD is frequently described in Asian patients [4] and there are only 13 case reports of Caucasians [10]. To the best of our knowledge this is the second case of NSD in the Italian population [5].
– HLA-B54/Cw1: is one of the diagnostic criteria for NSD [6], but in our case, as in other Caucasian patients, it was negative. HLA typing resulted positive for HLA-B07/B49/C07, which is different from those reported in Asians. Other Caucasian cases have not been tested for HLA typing [10].
Given the rarity of NSD, it is understandable that the correct diagnosis is not immediately achieved. The present case reinforces the value of an early evaluation of neurological symptoms in SD in order to achieve NSD diagnosis, allow the prompt initiation of the appropriate treatment and achieve successful therapeutic management [9]. A correct understanding of the neurological variant of the NSD remains a great challenge.
Conflict of interest None.
44
Letter to the Editor
References [1] P.R. Cohen, Sweet's syndrome–a comprehensive review of an acute febrile neutrophilic dermatosis, Orphanet J. Rare Dis. 2 (2007) 34. [2] J.J. Going, S.M. Going, M.W. Myśkoẃ, G.W. Beveridge, Sweet's syndrome: histological and immunohistochemical study of 15 cases, J. Clin. Pathol. 40 (1987) 175–179. [3] M. Mizoguchi, K. Matsuki, M. Mochizuki, et al., Human leukocyte antigen in Sweet's syndrome and its relationship to Behçet's disease, Arch. Dermatol. 124 (1988) 1069–1073. [4] K. Hisanaga, Y. Iwasaki, Y. Itoyama, Neuro-Sweet disease clinical manifestations and criteria for diagnosis, Neurology 64 (2005) 1756–1761. [5] F. Drago, G. Ribizzi, G. Ciccarese, et al., Recurrent episodes of neuro-Sweet syndrome in a Caucasian patient, J. Am. Acad. Dermato. 71 (2014) 192–193. [6] F. Niwa, T. Tokuda, M. Kimura, et al., Self-remitting and reversible parkinsonism associated with neuro-Sweet disease, Intern. Med. 49 (2010) 1201–1204. [7] K. Hisanaga, M. Hosokawa, N. Sato, et al., “Neuro-Sweet disease”: benign recurrent encephalitis with neutrophilic dermatosis, Arch. Neurol. 56 (1999) 1010–1013. [8] P.R. Cohen, R. Kurzrock, Sweet's syndrome and cancer, Clin. Dermatol. 11 (1993) 149–157. [9] J.F. Liu, Y. Li, K. Li, et al., Neuro-Sweet disease with positive modified acid-fast staining of the cerebrospinal fluid: a case report, Exp. Ther. Med. 11 (2016) 1239–1242. [10] F. Drago, G. Ciccarese, A.F. Agnoletti, et al., Neuro Sweet syndrome: a systematic review. A rare complication of Sweet syndrome, Acta Neurol Belg (2016 Sep 22) Epub ahead of print.
Greta Macorig Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Maria Elena Pessa Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Giuliano Barbarino Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy
Simona Scalise Department of Neurosciences, University of Rome Tor Vergata, viale Oxford 81, Roma, Italy Serena D'Agostini Neuroradiology Unit, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Mariarosaria Valente Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Gian Luigi Gigli Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Anna Scalise⁎ Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Corresponding author. E-mail address: [email protected] 3 September 2016 Available online 12 October 2016
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Neuro-Sweet disease: A diagnostic challenge Keywords: Neuro-Sweet disease Migraine Magnetic resonance imaging
1. Introduction Sweet disease (SD), also known as acute febrile neutrophilic dermatosis, is an inflammatory dermatologic disease, characterized by malaise, fever, leukocytosis and cutaneous edematous erythematous plaques that heal without scarring [1]. Skin biopsy of lesions reveal deep dermal infiltration of mature neutrophils and the absence of vasculitis [2]. The etiopathogenesis is unknown; however an association with HLA-B54 and HLA-Cw1 has been reported [3]. SD with central nervous system involvement has been reported as Neuro-Sweet disease (NSD) [4]. The most common neurological manifestation is encephalitis and meningitis, but headache, consciousness disturbance, epilepsy, involuntary movements, parkinsonism, paresthesias, hemiparesis or tetraparesis have been reported [4–6]. Cerebrospinal fluid examination (CSF) might show a mild increase in protein and mild pleocytosis, with a predominance of lymphocytes. Brain magnetic resonance imaging (MRI) could demonstrate abnormal alterations mainly in basal ganglia, thalamus, brainstem and less frequently in subcortical white matter [4,7]. Systemic corticosteroid therapy is highly effective for the treatment of NSD, otherwise other drugs (potassium-iodide, colchicine, dapsone, indomethacin and ciclosporin) could be used as a second option [1]. Usually, NSD is benign with rare neurological sequelae, however, there is a high frequency of symptom relapse, with persistent lesions on brain MRI [4]. The diagnosis of NSD is not easily achieved; often a misdiagnosis of other systemic autoimmune disease is made. We report the case of an Italian woman with SD, early atypical neurological involvement, multiple cortical-subcortical lesions in brain MRI and negative HLA-B54/Cw1.
2. Case report A 52-year-old woman, with migraine since her adolescence, presented with painful erythematous vesicles, weakness, fever and arthralgia. These symptoms were preceded by a respiratory infection. Skin lesions were detected asymmetrically on the upper trunk and limbs. Laboratory tests showed no abnormalities. Skin biopsy revealed acute neutrophilic dermatoses and allowed a Sweet disease diagnose. She
http://dx.doi.org/10.1016/j.jns.2016.10.012 0022-510X/© 2016 Published by Elsevier B.V.
was treated with Metylprednisolone 40 mg/die for seven days, then tapered, and her symptoms disappeared. Five months after the onset of Sweet disease the patient came to our attention complaining weakness, left hemisoma hyposthenia and headache, described unusual and non-responder to common drugs. Her neurological examination showed a mild impairment of the left pyramidal tract. No skin lesions were detected. A brain MRI revealed multiple hyperintense lesions in the corticalsubcortical junction in frontal and temporal regions bilaterally, without Gadolinium enhancement or diffusion restriction (Fig. 1A–B). Her cervical MRI did not present abnormalities. CSF showed a mild increase in protein and 2 lymphocytes. Oligoclonal bands were detected with a type 4 pattern, indicating systemic inflammation. Typing for HLA resulted negative for HLA-B51/B54/Cw1, but positive for HLA-B07/B49/C07. No abnormalities in routine nerve conduction studies were found. Tumor marker tests revealed no evidence of malignancy. She was retreated with corticosteroid therapy (Prednisone 60 mg die for 6 weeks) and recovered. Considering her history, symptoms, the MRI and CFS findings and her good response to steroid therapy, according to published criteria [4], the diagnosis of probable Neuro-Sweet disease was made. When the steroid therapy was gradually tapered, the patient complained relapse of the usual symptoms. At 7-month follow-up the patient had relapse of migraine and her MRI showed a new hyperintense lesion in the left frontal semioval center and confirmed the previously described lesions, all without Gadolinium enhancement or diffusion restriction (Fig. 1C–D). At 2-year follow-up the patient had a new relapse of migraine episodes and arthralgia, MRI was unchanged and CFS still showed mild increase in protein. We explained to the patient that preventive therapy for relapse remains to be established. We have, therefore, decided to treat migraine with specific therapy (Topiramate 25 mg die) and possibly use corticosteroid therapy only for relapses. The patient responded well.
3. Discussion The patient presented clinical features of cutaneous manifestation of SD but sub-sequentially showed an atypical neurological involvement, suggesting a systemic autoimmune disease. There is frequent overlap between NSD and other autoimmune diseases (Multiple sclerosis, Beҫhet disease, Systemic Lupus Erythematous, Chron's disease) and it could be also associated to malignancies and drug exposure [1,8]. In this case we ruled out these conditions. In particular, we excluded a demyelinating disease because this diagnose was not supported by MRI and CFS findings. Beҫhet disease was excluded because of the absence of cutaneous vasculitis, thrombosis in skin biopsy and the negative HLA-B51 typing.
Letter to the Editor
43
Fig. 1. (A–B) Hyperintense lesions in white matter, cortical-subcortical junction. FLAIR. ADC. (C–D) 7 month follow-up: new hyperintense lesion in frontal left white matter. FLAIR.
We considered the diagnosis of probable NSD on the basis of skin lesions with neutrophilic infiltrate, the detection of albumin-cytologic dissociation on CFS with oligoclonal bands positive for type 4 (characteristic of systemic inflammation), multiple hyperintense lesions in the cortical-subcortical regions and the clinical improvement after low dosage oral steroid therapy. The diagnosis requested some weeks and was attended by different specialists, in particular the Dermatologist and Neuroradiologist. Although our patient fulfilled most of the diagnostic criteria for NSD [4], her case seems atypical, due to: – onset and manifestations: in most case reports [4] the clinical onset is an aseptic meningo-encephalitis associated to cutaneous manifestations. Our patient complained migraine and pyramidal syndrome after the SD diagnosis, which is reported in 44,9% of cases [10]; – MRI: typical lesion sites in NSD are in basal ganglia, thalamus and brainstem [4], in this case lesions were detected in frontal and temporal regions bilaterally; – race: NSD is frequently described in Asian patients [4] and there are only 13 case reports of Caucasians [10]. To the best of our knowledge this is the second case of NSD in the Italian population [5].
– HLA-B54/Cw1: is one of the diagnostic criteria for NSD [6], but in our case, as in other Caucasian patients, it was negative. HLA typing resulted positive for HLA-B07/B49/C07, which is different from those reported in Asians. Other Caucasian cases have not been tested for HLA typing [10].
Given the rarity of NSD, it is understandable that the correct diagnosis is not immediately achieved. The present case reinforces the value of an early evaluation of neurological symptoms in SD in order to achieve NSD diagnosis, allow the prompt initiation of the appropriate treatment and achieve successful therapeutic management [9]. A correct understanding of the neurological variant of the NSD remains a great challenge.
Conflict of interest None.
44
Letter to the Editor
References [1] P.R. Cohen, Sweet's syndrome–a comprehensive review of an acute febrile neutrophilic dermatosis, Orphanet J. Rare Dis. 2 (2007) 34. [2] J.J. Going, S.M. Going, M.W. Myśkoẃ, G.W. Beveridge, Sweet's syndrome: histological and immunohistochemical study of 15 cases, J. Clin. Pathol. 40 (1987) 175–179. [3] M. Mizoguchi, K. Matsuki, M. Mochizuki, et al., Human leukocyte antigen in Sweet's syndrome and its relationship to Behçet's disease, Arch. Dermatol. 124 (1988) 1069–1073. [4] K. Hisanaga, Y. Iwasaki, Y. Itoyama, Neuro-Sweet disease clinical manifestations and criteria for diagnosis, Neurology 64 (2005) 1756–1761. [5] F. Drago, G. Ribizzi, G. Ciccarese, et al., Recurrent episodes of neuro-Sweet syndrome in a Caucasian patient, J. Am. Acad. Dermato. 71 (2014) 192–193. [6] F. Niwa, T. Tokuda, M. Kimura, et al., Self-remitting and reversible parkinsonism associated with neuro-Sweet disease, Intern. Med. 49 (2010) 1201–1204. [7] K. Hisanaga, M. Hosokawa, N. Sato, et al., “Neuro-Sweet disease”: benign recurrent encephalitis with neutrophilic dermatosis, Arch. Neurol. 56 (1999) 1010–1013. [8] P.R. Cohen, R. Kurzrock, Sweet's syndrome and cancer, Clin. Dermatol. 11 (1993) 149–157. [9] J.F. Liu, Y. Li, K. Li, et al., Neuro-Sweet disease with positive modified acid-fast staining of the cerebrospinal fluid: a case report, Exp. Ther. Med. 11 (2016) 1239–1242. [10] F. Drago, G. Ciccarese, A.F. Agnoletti, et al., Neuro Sweet syndrome: a systematic review. A rare complication of Sweet syndrome, Acta Neurol Belg (2016 Sep 22) Epub ahead of print.
Greta Macorig Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Maria Elena Pessa Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Giuliano Barbarino Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy
Simona Scalise Department of Neurosciences, University of Rome Tor Vergata, viale Oxford 81, Roma, Italy Serena D'Agostini Neuroradiology Unit, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Mariarosaria Valente Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Gian Luigi Gigli Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Anna Scalise⁎ Neurology Clinic, University Hospital Santa Maria della Misericordia, p.le Santa Maria della Misericordia 15,Udine, Italy Corresponding author. E-mail address: [email protected] 3 September 2016 Available online 12 October 2016