**6. Conclusion**

The analysis provides a focused review of clinical manifestations, diagnosis, and treatment of OM and highlights the significant limitations of the literature. Diagnosis of OM is generally straightforward, when the clinician thinks of the disorder. Confirmation of clinical diagnosis is challenging for OM. Serum AChR antibodies are found in only half of patients, and while the MuSK antibody is detected in about three percent of the generalized MG population, it is found only rarely among patients with isolated OM. Therefore the majority of patients lack detectable autoantibodies and confirmation of a neuromuscular transmission disorder relies on specialized, electrophysiological testing. Although expert opinion suggests that treatment is highly effective, significant knowledge gaps exist as to severity of treatment complications and over-all quality of life of patients with OM. Only through prospective trials or multi-center, rigorously constructed outcome databases will improvements in treatment be achieved.

Ocular Myasthenia Analysis of Diagnostic and Treatment Options 115

Cogan, D. (1965). Myasthenia gravis: a review of the disease and a description of lid twitch

Conti-Fine, B. M., Milani, M. and Kaminski, H. J. (2006). Myasthenia gravis: past, present,

Daroff, R. and Benatar, M. (2009). Ocular Myasthenia. Myasthenia Gravis and Related

Daroff, R. B. (1986). The office tensilon test for ocular myasthenia gravis. *Arch Neurol* 43: pp.

de Entrambasaguas, M., Lopez-Bernabe, R. and Lopez-Alemany, M. (2007). [Ocular

Ellis, F. D., Hoyt, C. S., Ellis, F. J., Jeffery, A. R. and Sondhi, N. (2000). Extraocular muscle

Elrod, R. D. and Weinberg, D. A. (2004). Ocular myasthenia gravis. *Ophthalmol Clin North* 

Evoli, A., Tonali, P., Bartoccioni, E. and LoMonaco, M. (1988). Ocular myasthenia: Diagnostic and therapeutic problems. *Acta Neurol Scand* 77: pp. 31-35. Evoli, A., Tonali, P. A., Padua, L., Monaco, M. L., Scuderi, F., Batocchi, A. P., Marino, M. and

Fouladvand, M., Ledoux, D. and Barton, J. S. (2005). Ocular Myasthenia Gravis.

Gilbert, M. E., De Sousa, E. A. and Savino, P. J. (2007). Ocular Myasthenia Gravis treatment: the case against prednisone therapy and thymectomy. *Arch Neurol* 64(12): pp. 1790-1792. Gilbert, M. E. and Savino, P. J. (2007). Ocular myasthenia gravis. *Int Ophthalmol Clin* 47(4):

Golnik, K. (1997). An ice test for the diagnosis of myasthenia gravis. *Ophthalmology* 106(7):

Golnik, K. C., Pena, R., Lee, A. G. and Eggenberger, E. R. (1999). An ice test for the diagnosis

Grob, D. (1999). Natural History of Myasthenia Gravis. Myasthenia Gravis and Myasthenic Disorders. A. G. Engel. New York, Oxford University Press: 131-154. Hawkins, B. R., Yu, Y. L., Wong, V., Woo, E., Ip, M. S. and Dawkins, R. L. (1989). Possible

Heckmann, J. M., Owen, E. P. and Little, F. (2007). Myasthenia gravis in South Africans:

Hirano, M. and DiMauro, S. (2001). ANT1, Twinkle, POLG, and TP: New genes open our

Hoch, W., McConville, J., Helms, S., Newsom-Davis, J., Melms, A. and Vincent, A. (2001).

gravis without acetylcholine receptor antibodies. *Nat Med* 7(3): pp. 365-368. Hohlfeld, R., Michels, M., Heininger, K., Besinger, U. and Toyka, K. V. (1988). Azathioprine

receptor antibody in Chinese patients. *Quart J Med* 70: pp. 235-241.

Racial differences in clinical manifestations. *Neuromuscul Disord*.

eyes to ophthalmoplegia. *Neurology* 57(12): pp. 2163-2165.

evidence of a variant of myasthenia gravis based on HLA and acetylcholine

Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia

toxicity during long-term immunosuppression of generalized myasthenia gravis.

seronegative myasthenia gravis. *Brain* 126(Pt 10): pp. 2304-2311.

of myasthenia gravis. *Ophthalmology* 106(7): pp. 1282-1286.

*Comprehensive Opthalmology Update* 6: pp. 25-36.

myasthenia gravis: diagnostic aspects and evolution]. *Rev Neurol* 44(7): pp. 397-403.

responses to orbital cooling (ice test) for ocular myasthenia gravis diagnosis. *J Aapos*

Bartoccioni, E. (2003). Clinical correlates with anti-MuSK antibodies in generalized

as a characteristic sign. *Arch Ophthalmol*(74): pp. 217–221.

Disorders. H. J. Kaminski. Totowa, NJ, Humana Press: 95-104.

and future. *J Clin Invest* 116(11): pp. 2843-2854.

843-844.

4(5): pp. 271-281.

pp. 93-103, ix.

pp. 1282-1286.

*Neurology* 38: pp. 258-261.

*Am* 17(3): pp. 275-309; v.

#### **7. References**


Agius, M. A. (2000). Treatment of ocular myasthenia with corticosteroids: yes. *Arch Neurol*

Argov, Z. (2010). Current approach to seronegative myasthenia. *Journal of Neurology* 258(1):

Barton, J. J. and Fouladvand, M. (2000). Ocular aspects of myasthenia gravis. *Semin Neurol*

Barton, J. J., Jama, A. and Sharpe, J. A. (1995). Saccadic duration and intrasaccadic fatigue in myasthenic and nonmyasthenic ocular palsies. *Neurology* 45(11): pp. 2065-2072. Beekman, R., Kuks, J. B. and Oosterhuis, H. J. (1997). Myasthenia gravis: diagnosis and

Benatar, M. (2006). A systematic review of diagnostic studies in myasthenia gravis.

Benatar, M. and Kaminski, H. J. (2007). Evidence report: the medical treatment of ocular

Bentley, C. R., Dawson, E. and Lee, J. P. (2001). Active management in patients with ocular

Bever, C. T., Aquino, A. V., Penn, A. S., Lovelace, R. E. and Rowland, L. P. (1983). Prognosis

Bhanushali, M. J., Wuu, J. and Benatar, M. (2008). Treatment of ocular symptoms in

Caress, J. B., Hunt, C. H. and Batish, S. D. (2005). Anti-MuSK myasthenia gravis presenting

Casetta, I., Groppo, E., Gennaro, R., Cesnik, E., Piccolo, L., Volpato, S. and Granieri, E.

Chan, J. W. and Orrison, W. W. (2007). Ocular myasthenia: a rare presentation with MuSK antibody and bilateral extraocular muscle atrophy. *Br J Ophthalmol* 91(6): pp. 842-843. Chan, K. H., Lachance, D. H., Harper, C. M. and Lennon, V. A. (2007). Frequency of

Chirapapaisan N, T. S., Chuenkongkaew W (2007). Factors associated with insensitivity to

Chiu, H.-C., Vincent, A., Nemsom-Davis, J., Hsieh, K.-H. and Hung, T.-p. (1987). Myasthenia

(2010). Myasthenia gravis: a changing pattern of incidence. *Journal of Neurology*

seronegativity in adult-acquired generalized myasthenia gravis. *Muscle & Nerve*

pyridostigmine therapy in Thai patients with ocular myasthenia gravis. *Asian Pac J* 

gravis: population differences in disease expression and acetylcholine receptor antibody titers between Chinese and Caucasians. *Neurology* 37: pp. 1854-1857. Christensen, P., Jensen, T., Tsiropoulos, I., Sorensen, T., Kjaer, M., Hojer-Pedersen, E.,

Rasmussen, M., Lehfeldt, E. and de Fine Olivarius, B. (1993). Incidence and prevalence of myasthenia gravis in western Denmark 1975 to 1989. *Neurology* 43:

of the American Academy of Neurology. *Neurology* 68(24): pp. 2144-2149. Bennett, D. L., Mills, K. R., Riordan-Eva, P., Barnes, P. R. and Rose, M. R. (2006). Anti-MuSK

manifestations of myasthenia gravis. *Eye* 15(Pt 1): pp. 18-22.

with purely ocular findings. *Arch Neurol* 62(6): pp. 1002-1003.

of ocular myasthenia. *Ann Neurol* 14: pp. 516-519.

myasthenia gravis. *Neurology* 71(17): pp. 1335-1341.

myasthenia (an evidence-based review): report of the Quality Standards Subcommittee

antibodies in a case of ocular myasthenia gravis. *J Neurol Neurosurg Psychiatry* 77(4):

follow-up of 100 consecutive patients. *J Neurol* 244(2): pp. 112-118.

**7. References** 

57(5): pp. 750-751.

pp. 14-18.

20(1): pp. 7-20.

pp. 564-565.

257(12): pp. 2015-2019.

36(5): pp. 651-658.

pp. 1779-1783.

*Allergy Immunol* 25(1): pp. 13-16.

*Neuromuscul Disord* 16(7): pp. 459-467.


Ocular Myasthenia Analysis of Diagnostic and Treatment Options 117

Matell, G. (1987). Immunosuppressive drugs: azathioprine in the treatment of myasthenia

Matsuda, M., Dohi-Iijima, N., Nakamura, A., Sekijima, Y., Morita, H., Matsuzawa, S., Sato,

Mee, J., Paine, M., Byrne, E., King, J., Reardon, K. and O'Day, J. (2003). Immunotherapy of

Mehndiratta, M. M., Pandey, S. and Kuntzer, T. (2011). Acetylcholinesterase inhibitor treatment for myasthenia gravis. *Cochrane Database Syst Rev* 2: pp. CD006986. Mercelis, R. and Merckaert, V. (2011). Diagnostic utility of stimulated single-fiber

Meriggioli, M. N. and Sanders, D. B. (2004). Myasthenia gravis: diagnosis. *Semin Neurol*

Mertens, H. G., Hertel, G., Reuther, P. and Ricker, K. (1981). Effect of immunosuppressive

Nicholson GA, M. J., Griffiths LR (1983). Comparison of diagnostic tests in myasthenia

Odell, J. G., Winterkorn, J. M. S. and Behrens, M. M. (1991). The sleep test for myasthenia gravis. Safe alternative to Tensilon. *J Clin Neuro Opthalmol* 11: pp. 288-292. Oh SJ, C. H. (1990). Edrophonium responsiveness not necessarily diagnostic of myasthenia

Oh SJ, K. D., Kuruoglu R, et al (1992). Diagnostic sensitivity of the laboratory tests in

Ohtsuki, H., Hasebe, S., Okano, M. and Furuse, T. (1996). Strabismus surgery in ocular

Oosterhuis, H. (1989). The natural course of myasthenia gravis. *J Neurol Neurosurg Psychiatry*

Palace, J., Newsom-Davis, J. and Lecky, B. (1998). A randomized double-blind trial of

Papapetropoulos, T. H., Ellul, J. and Tsibri, E. (2003). Development of generalized

Phillips, L., Torner, J., Anderson, M. and Cox, G. (1992). The epidemiology of myasthenia

Phillips, L. H. and Torner, J. C. (1996). Epidemiologic evidence for a changing natural

Roberts, P. F., Venuta, F., Rendina, E., De Giacomo, T., Coloni, G. F., Follette, D. M.,

Roh, H. S., Lee, S. Y. and Yoon, J. S. (2011). Comparison of clinical manifestations between

gravis in central and western Virginia. *Neurology* 42: pp. 1888-1893.

prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis

myasthenia gravis in patients with ocular myasthenia gravis. *Arch Neurol* 60(10):

Richman, D. P. and Benfield, J. R. (2001). Thymectomy in the treatment of ocular

patients with ocular myasthenia gravis and generalized myasthenia gravis. *Korean J* 

myasthenia gravis. *Muscle Nerve*(15): pp. 720–724. indentation

myasthenia gravis. *Ophthalmologica* 210(2): pp. 95-100.

Pascuzzi, R. M. (2003). The edrophonium test. *Semin Neurol* 23(1): pp. 83-88.

history of myasthenia gravis. *Neurology* 47: pp. 1233-1238.

myasthenia gravis. *J Thorac Cardiovasc Surg* 122(3): pp. 562-568.

Study Group. *Neurology* 50(6): pp. 1778-1783.

S., Yahikozawa, H., Tabata, K., Yanagawa, S. and Ikeda, S. (2005). Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture,

ocular myasthenia gravis reduces conversion to generalized myasthenia gravis. *J* 

electromyography of the orbicularis oculi muscle in patients with suspected ocular

gravis. *Ann N Y Acad Sci* 505: pp. 589-594.

Japan. *Intern Med* 44(6): pp. 572-577.

*Neuroophthalmol* 23(4): pp. 251-255.

gravis. *Clin Exp Neurol*(19): pp. 45-49.

gravis. *Muscle Nerve*(13): pp. 187-191.

24(1): pp. 31-39.

52: pp. 1121-1127.

pp. 1491-1492.

*Ophthalmol* 25(1): pp. 1-7.

myasthenia. *Muscle & Nerve* 43(2): pp. 168-170.

drugs (azathioprine). *Ann N Y Acad Sci* 377: pp. 691-699.


Howard, F. J., Lennon, V., Finley, J., Matsumoto, J. and Elveback, L. (1987). Clinical

Ing, E. B., Ing, S. Y., Ing, T. and Ramocki, J. A. (2000). The complication rate of edrophonium

Kaminski, H. J. and Daroff, R. B. (2000). Controversies in Neurology. Treatment of ocular myasthenia: steroids only when compelled. *Arch Neurol* 57: pp. 752-753. Katirji, B. and Kaminski, H. J. (2002). An electrodiagnostic approach to the patient with

Khanna, S., Liao, K., Kaminski, H. J., Tomsak, R. L., Joshi, A. and Leigh, R. J. (2007). Ocular

Kubis, K. C., Danesh-Meyer, H. V., Savino, P. J. and Sergott, R. C. (2000). The ice test versus the rest test in myasthenia gravis. *Ophthalmology* 107(11): pp. 1995-1998. Kuks, J. and Oosterhuis, H. J. G. H. (2003). Clinical Presentation and Epidemiology of

Kupersmith, M. J. (2004). Does early treatment of ocular myasthenia gravis with prednisone reduce progression to generalized disease? *J Neurol Sci* 217(2): pp. 123-124. Kupersmith, M. J., Latkany, R. and Homel, P. (2003). Development of generalized disease at 2 years in patients with ocular myasthenia gravis. *Arch Neurol* 60(2): pp. 243-248. Kupersmith, M. J. and Ying, G. (2005). Ocular motor dysfunction and ptosis in ocular myasthenia gravis: effects of treatment. *Br J Ophthalmol* 89(10): pp. 1330-1334. Kusner, L. L., Puwanant, A. and Kaminski, H. J. (2006). Ocular myasthenia: diagnosis,

Leigh, R. J. and Zee, D. S. (1999). The Neurology of Eye Movements. Philadelphia, F.A. Davis. Leite, M. I., Jacob, S., Viegas, S., Cossins, J., Clover, L., Morgan, B. P., Beeson, D., Willcox, N.

Lennon, V. (1997). Serologic profile of myasthenia gravis and distinction from Lambert-

Liyanage, Y., Hoch, W., Beeson, D. and Vincent, A. (2002). The agrin/muscle-specific kinase

Luchanok, U. and Kaminski, H. J. (2008). Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. *Curr Opin Neurol* 21(1): pp. 8-15. MacDonald, B. K., Cockerell, O. C., Sander, J. W. and Shorvon, S. D. (2000). The incidence

Mantegazza, R., Antozzi, C., Peluchetti, D., Sghirlanzoni, A. and Cornelio, F. (1988).

Mantegazza, R., Baggi, F., Antozzi, C., Confalonieri, P., Morandi, L., Bernasconi, P.,

Eaton myasthenic syndrome. *Neurology* 48 (Suppl 5): pp. S23-27.

receptors in myasthenia gravis. *Ann NY Acad Sci* 505: pp. 526-538.

neuromuscular junction disorder. *Neur Clin* 20: pp. 557-586.

treatment, and pathogenesis. *Neurologist* 12(5): pp. 231-239.

myasthenia gravis. *Brain* 131(7): pp. 1940-1952.

based study in the UK. *Brain* 123(Pt 4): pp. 665-676.

myasthenia gravis. *J Neurol* 235: pp. 449-453.

*Acad Sci* 998: pp. 413-423.

junction. *Muscle Nerve* 25(1): pp. 4-16.

discussion 145.

*of Neurology* 254(11): pp. 1569-1574.

Totowa, NJ, Humana Press: 93-114.

correlations of antibodies that bind, block, or modulate human acetylcholine

testing for suspected myasthenia gravis. *Can J Ophthalmol* 35(3): pp. 141-144;

myasthenia revisited: Insights from pseudo-internuclear ophthalmoplegia. *Journal* 

Myasthenia Gravis. Myasthenia Gravis and Related Disorders. H. J. Kaminski.

and Vincent, A. (2008). IgG1 antibodies to acetylcholine receptors in 'seronegative'

pathway: new targets for autoimmune and genetic disorders at the neuromuscular

and lifetime prevalence of neurological disorders in a prospective community-

Azathioprine as a single drug or in combination with steroids in the treatment of

Andreetta, F., Simoncini, O., Campanella, A., Beghi, E. and Cornelio, F. (2003). Myasthenia gravis (MG): epidemiological data and prognostic factors. *Ann N Y* 


Sanders, D. B. (2004). Electrophysiologic tests of neuromuscular transmission. *Suppl Clin Neurophysiol* 57: pp. 167-169.

**7** 

*Spain* 

**Sweet Syndrome** 

Manuel Ginarte and Jaime Toribio

*Faculty of Medicine. Santiago de Compostela,* 

*Department of Dermatology. Complejo Hospitalario Universitario de Santiago.* 

Sweet syndrome (SS) was first described by Robert Sweet in 1964 as acute febrile neutrophilic dermatosis (Sweet, 1966). Despite of the descriptive value of this denomination and the advice of Robert Sweet to keep it, the eponymous became prevalent on the time. SS was the first neutrofilic dermatosis (ND) described and it represents the paradigm of them. There are three key points of SS that are of interest not only for the dermatologists but also for the general practitioners: a) its marked clinical manifestations, b) the potential systemic repercussion of neutrophilic reaction, and c) its association with extracutaneos diseases,

SS is a neutrophilic dermatosis characterized by specific clinical and histopathological manifestations. In fact, the best way of defining SS is based on its diagnostic criteria. Typically, SS appears abruptly with multiple, edematous, tender red plaques that are distributed bilaterally but asymmetrically in a febrile patient. The dermatopathological image shows a neutrophilic diffuse infiltrate without vasculitis located in upper dermis. Besides this typical picture, several clinical and histopathological variants have been described (table 1). The current classification of SS is based on the associated or trigger

conditions and has clinical value for the management of these patients (table 2).

Table 1. Main clinical and histopathological subtypes of Sweet syndrome

Transitional forms with other neutrophlic dermatosis

Located forms: dorsal hands and facial Chronic recurrent neutrophilic dermatosis

Histiocytoid Sweet syndrome

Idiopatic

Parainflammatory Paraneoplastic Drug-induced

Associated to pregnancy

Table 2. Classification of Sweet syndrome

**1. Introduction** 

especially with malignancies.

**2. Definition and classification** 

