- Email: [email protected]
Dermatomyositis and concomitant overlap myasthenic syndrome: A rare presentation
e150 Letters
Fig 1. Nonblanching pink and light brown patches on forehead and right temple.
J AM ACAD DERMATOL
NOVEMBER 2011
which an erythematous, purpuric, or urticarial rash appears on the lower extremities following major muscular activity or exercise.3 Almost all reports of exercise-induced vasculitis occur in patients older than 50 years of age and involve aerobic activity, such as walking,3 running,4 and golfing,5 though one report showed chest and back involvement in an 11-year-old boy following intense basketball training.6 Importantly, the histopathologic findings of our patient’s lesions were consistent with those of a capillaritis and not a leukocytoclastic vasculitis, which distinguishes progressive pigmentary purpura from exercise-induced vasculitis, respectively.5 Charlotte Hwa, BA, Jeremy A. Brauer, MD, Jyoti P. Mundi, MD, Julie M. Wu, MD, Rishi R. Patel, MD, Alan Greenspan, MD, and Jennifer A. Stein, MD, PhD Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
Fig 2. Superficial perivascular lymphocytic infiltrate with scattered extravasated erythrocytes, focal perivascular fibrin deposition, and solar elastosis within the dermis. (Hematoxylin-eosin stain; original magnification: 3200.)
The etiology of the pigmented purpuric eruptions remains unclear. While exercise has been suggested as an etiologic factor,1 to the authors’ knowledge, no prior reports have linked exercise with biopsy-proven progressive pigmentary purpura. Gravitational dependency and venous pressure have been thought to play a role in lesion localization since the purpuric rash commonly appears on the lower legs. Whether or not the different yoga positions may have played a role in affecting lesion localization in our patient is unknown. A background of sun damage, as shown by the solar elastosis in our patient’s histopathologic findings, may have contributed to a decreased ability of the connective tissue to support the capillaries. This is consistent with a previous report, which showed solar purpura occurring in relation to a jog under the midday sun2; however, the development of our patient’s lesions was not associated with acute sun exposure as described in that particular case. Our patient demonstrates that exercise may play an important etiologic role in progressive pigmentary purpura. On the differential diagnosis is exercise-induced purpura, also known as exercise-induced vasculitis, a distinct entity in
Dr Stein was supported by the Irwin I. Lubowe Fellowship in Dermatology. Conflicts of interest: None declared. Reprint requests to: Jennifer A. Stein, MD, PhD, 560 First Avenue, H-100, New York, NY 10016. E-mail: [email protected] REFERENCES 1. Allan SJ, Humphreys F, Buxton PK. Annular purpura and step aerobics. Clin Exp Dermatol 1994;19:418. 2. Latenser BA, Hempstead RW. Exercise-associated solar purpura in an atypical location. Cutis 1985;35:365-6. 3. Ramelet AA. Exercise-induced vasculitis. J Eur Acad Dermatol Venereol 2006;20:423-7. 4. Mailler-Savage EA, Adams BB. Skin manifestations of running. J Am Acad Dermatol 2006;55:290-301. 5. Kelly RI, Opie J, Nixon R. Golfer’s vasculitis. Australas J Dermatol 2005;46:11-4. 6. Leung AK, Grant RM, Truscott R. Exercise-induced purpura. J Sports Med Phys Fitness 1990;30:329-30. doi:10.1016/j.jaad.2011.07.027
Dermatomyositis and concomitant overlap myasthenic syndrome: A rare presentation To the Editor: Both dermatomyositis (DM) and overlap myasthenic syndrome (OMS) may herald internal malignancy but, to our knowledge, have never been reported to occur concomitantly. While proximal muscle weakness is common to both diseases, OMS, which is an overlap of Lambert-Eaton myasthenic syndrome and myasthenia gravis, also can cause respiratory failure, ophthalmoplegia, and
J AM ACAD DERMATOL VOLUME 65, NUMBER 5
Fig 1. Erythema over joints of dorsal hand.
areflexia.1,2 We report a patient with combined DM and OMS who was ultimately diagnosed with ductal carcinoma of the breast. A 67-year-old woman was transferred to our institution for progressive weakness and shortness of breath. Eight weeks before admission, she developed a mildly pruritic, patchy rash that started on the chest and progressed to the proximal extremities and back of hands. Two weeks before admission, she began having dysphagia and facial weakness. She was empirically placed on pyridostigmine without improvement. She then developed rapidly progressive cranial, bulbar, and proximal limb muscle weakness with respiratory distress. Upon admission, she was intubated and found to have a 25% cardiac ejection, but normal coronary arteries by catheterization. Physical examination revealed erythematous patches scattered over the back of her shoulders, upper aspect of her back, thighs, and overlying the joints of the dorsal hands (Fig 1). Neurologic examination showed bilateral facial paresis, ophthalmoplegia, proximal muscle weakness, and areflexia. Initial laboratory testing was significant for an elevated creatine kinase (1178 U/L; normal 25-190 U/L), and aldolase (24 U/L; normal \8.1 U/L). Jo-1, double-stranded DNA, SS-A, SS-B, and Mi-2 antibodies were negative. Nerve conduction studies showed diffusely low compound motor amplitudes with normal velocities, F waves, and latencies. Electromyography showed active myopathy. A skin biopsy specimen of her right shoulder revealed vacuolar interface dermatitis, rare dyskeratotic keratinocytes, and slight increase in dermal mucin, consistent with DM (Fig 2). Biopsy specimen of the biceps muscle was indicative of severe inflammatory myopathy. Initial malignancy workup, including chest, abdomen, and pelvis computed tomography scans and CA125, revealed negative findings. The presence of craniobulbar weakness, areflexia, and low compound motor amplitudes, not usually
Letters e151
Fig 2. Vacuolar interface dermatitis, rare dyskeratotic keratinocytes, and slight increase in dermal mucin. (Hematoxylin-eosin stain.) The authors acknowledge Aleador Andea, MD, for the photomicrograph.
found in DM, suggested a concomitant neuromuscular junction disorder. This possibility was supported by serologic identification of P/Q-type voltage-gated calcium channel antibodies (0.15 nmol/L; normal \0.02 nmol/L), acetylcholine receptor binding antibodies (0.17 nmol/L; normal \0.02 nmol/L), and acetylcholine receptor modulating antibodies (42% loss of acetylcholine receptor; normal 0%-20%). Although repetitive nerve stimulation was not performed, the combined clinical and serologic findings were most consistent with OMS. The patient was treated with intravenous immunoglobulin and Solu-Medrol with neurologic improvement. Six months after discharge, she was noted to have an abnormal mammogram and was subsequently diagnosed with invasive ductal breast carcinoma. To our knowledge, this is the first report of an association between DM and OMS. Both diseases are autoimmune in origin, and have identifiable autoantibodies, although testing for the anti155/140 and anti-CADM-140 antibodies of DM3 were not performed on this patient. Both diseases may also be paraneoplastic in nature. The most common underlying malignancies in DM are colon, ovarian, breast, gastric, or lymphoma,4 with breast, uterine, and ovarian cancer in women being overrepresented in previous reports.5 OMS has previously been associated with small-cell lung cancer6 but not with breast cancer. The rash, proximal muscle weakness, respiratory failure, ophthalmoplegia, and areflexia produced an unusual and diagnostically challenging picture in this acutely ill patient. Dermatologists and neurologists should be aware of the coexistence of these treatable paraneoplastic disorders. Erika K. Hill, MD,a Peter H. King, MD,b,c and Lauren C. Hughey, MDa
J AM ACAD DERMATOL
e152 Letters
NOVEMBER 2011
Departments of Dermatologya and Neurology,b University of Alabama at Birmingham; and Birmingham Veterans Affairs Medical Centerc Funding sources: None. Conflicts of interest: None declared. Correspondence to: Lauren C. Hughey, MD, Department of Dermatology, University of Alabama at Birmingham, 1530 Third Ave S, EFH 414, Birmingham, AL 35294 E-mail: [email protected] REFERENCES 1. Newsom-Davis J, Leys K, Vincent A, Ferguson I, Modi G, Mills K. Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. J Neurol Neurosurg Psychiatry 1991;54: 452-3. 2. Oh SJ, Sher E. MG and LEMS overlap syndrome: case report with electrophysiological and immunological evidence. Clin Neurophysiol 2005;116:1167-71. 3. Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T, et al. Clinical correlations with dermatomyositisspecific autoantibodies in adult Japanese patients with dermatomyositis. Arch Dermatol 2011;147:391-8. 4. Hill C, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 2001; 357:96-100. 5. Leandro MJ, Isenberg DA. Rheumatic diseases and malignancyeis there an association? Scand J Rheumatol 2001;30: 185-8. 6. Leger JM, Bachoud-Levi AC, Eymard B, Theodore C, Bouche P, Pierrot-Deseilligny C. Paraneoplastic myasthenic syndrome. Rev Neurol (Paris) 1993;149:485-8. doi:10.1016/j.jaad.2011.07.028
Detection of Merkel cell polyomavirus in cutaneous squamous cell carcinoma before occurrence of Merkel cell carcinoma To the Editor: In 2008, a previously unknown polyomavirus, Merkel cell polyomavirus (MCPyV), was identified in Merkel cell carcinoma (MCC) lesions and close association between MCPyV and MCC has been suggested.1,2 However, to our knowledge, no previous reports have confirmed MCPyV infection in patients with MCC before the occurrence of MCC. We herein report a patient who developed squamous cell carcinoma (SCC) followed by MCC. MCPyV was detected in both tumors by polymerase chain reaction analysis. A 78-year-old Japanese man who had been immunosuppressed as a result of diabetes mellitus noticed a nodule on his right cheek, and the tumor was simply resected (Fig 1, A). The tumor was
Fig 1. Squamous cell carcinoma (SCC) on right cheek (A) and Merkel cell carcinoma (MCC) in left axilla (B). A, Patient presented with crater-shaped nodule on right cheek (arrow). Resected tumor was typical, moderately differentiated SCC. B, Positron emission computed tomography showed solid mass 10 3 30 mm in size in left axilla (white arrow). Histopathologically, lesion was diagnosed as nodal MCC.
diagnosed histopathologically as typical SCC. Coexisting MCC was not found anywhere in the resected specimen by either hematoxylin-eosin stain or immunostaining for cytokeratin 20. One year later, he presented with a subcutaneous nodule in his left axillary lymph node. Positron emission computed tomography showed a solid mass (Fig 1, B). Histopathological, immunohistochemical, and ultrastructural examination revealed that the tumor was a nodal MCC, although the primary lesion was not discovered. Fourteen months after the axillary dissection, he developed multiple metastatic MCC lesions and died 10 months later. The VP1 region of MCPyV DNA was amplified from DNA samples both of the MCC and the SCC lesions (Fig 2, A). Copy numbers of MCPyV DNA large tumor (LT) domain were determined by quantitative real-time polymerase chain reaction using the b-globin gene as an internal control. The MCPyVLT/b-actin in the MCC sample was 3.9 3 104/4.8 3 105 (¼8.1 3 102 copies per cell), and that in the SCC sample was 8.1 3 102/2.0 3 103 (¼4.0 3 103 copies per cell). Larger copy numbers of viral genome were obtained in the MCC lesion. Immunohistochemical staining demonstrated that the MCC cells were
Fig 1. Nonblanching pink and light brown patches on forehead and right temple.
J AM ACAD DERMATOL
NOVEMBER 2011
which an erythematous, purpuric, or urticarial rash appears on the lower extremities following major muscular activity or exercise.3 Almost all reports of exercise-induced vasculitis occur in patients older than 50 years of age and involve aerobic activity, such as walking,3 running,4 and golfing,5 though one report showed chest and back involvement in an 11-year-old boy following intense basketball training.6 Importantly, the histopathologic findings of our patient’s lesions were consistent with those of a capillaritis and not a leukocytoclastic vasculitis, which distinguishes progressive pigmentary purpura from exercise-induced vasculitis, respectively.5 Charlotte Hwa, BA, Jeremy A. Brauer, MD, Jyoti P. Mundi, MD, Julie M. Wu, MD, Rishi R. Patel, MD, Alan Greenspan, MD, and Jennifer A. Stein, MD, PhD Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
Fig 2. Superficial perivascular lymphocytic infiltrate with scattered extravasated erythrocytes, focal perivascular fibrin deposition, and solar elastosis within the dermis. (Hematoxylin-eosin stain; original magnification: 3200.)
The etiology of the pigmented purpuric eruptions remains unclear. While exercise has been suggested as an etiologic factor,1 to the authors’ knowledge, no prior reports have linked exercise with biopsy-proven progressive pigmentary purpura. Gravitational dependency and venous pressure have been thought to play a role in lesion localization since the purpuric rash commonly appears on the lower legs. Whether or not the different yoga positions may have played a role in affecting lesion localization in our patient is unknown. A background of sun damage, as shown by the solar elastosis in our patient’s histopathologic findings, may have contributed to a decreased ability of the connective tissue to support the capillaries. This is consistent with a previous report, which showed solar purpura occurring in relation to a jog under the midday sun2; however, the development of our patient’s lesions was not associated with acute sun exposure as described in that particular case. Our patient demonstrates that exercise may play an important etiologic role in progressive pigmentary purpura. On the differential diagnosis is exercise-induced purpura, also known as exercise-induced vasculitis, a distinct entity in
Dr Stein was supported by the Irwin I. Lubowe Fellowship in Dermatology. Conflicts of interest: None declared. Reprint requests to: Jennifer A. Stein, MD, PhD, 560 First Avenue, H-100, New York, NY 10016. E-mail: [email protected] REFERENCES 1. Allan SJ, Humphreys F, Buxton PK. Annular purpura and step aerobics. Clin Exp Dermatol 1994;19:418. 2. Latenser BA, Hempstead RW. Exercise-associated solar purpura in an atypical location. Cutis 1985;35:365-6. 3. Ramelet AA. Exercise-induced vasculitis. J Eur Acad Dermatol Venereol 2006;20:423-7. 4. Mailler-Savage EA, Adams BB. Skin manifestations of running. J Am Acad Dermatol 2006;55:290-301. 5. Kelly RI, Opie J, Nixon R. Golfer’s vasculitis. Australas J Dermatol 2005;46:11-4. 6. Leung AK, Grant RM, Truscott R. Exercise-induced purpura. J Sports Med Phys Fitness 1990;30:329-30. doi:10.1016/j.jaad.2011.07.027
Dermatomyositis and concomitant overlap myasthenic syndrome: A rare presentation To the Editor: Both dermatomyositis (DM) and overlap myasthenic syndrome (OMS) may herald internal malignancy but, to our knowledge, have never been reported to occur concomitantly. While proximal muscle weakness is common to both diseases, OMS, which is an overlap of Lambert-Eaton myasthenic syndrome and myasthenia gravis, also can cause respiratory failure, ophthalmoplegia, and
J AM ACAD DERMATOL VOLUME 65, NUMBER 5
Fig 1. Erythema over joints of dorsal hand.
areflexia.1,2 We report a patient with combined DM and OMS who was ultimately diagnosed with ductal carcinoma of the breast. A 67-year-old woman was transferred to our institution for progressive weakness and shortness of breath. Eight weeks before admission, she developed a mildly pruritic, patchy rash that started on the chest and progressed to the proximal extremities and back of hands. Two weeks before admission, she began having dysphagia and facial weakness. She was empirically placed on pyridostigmine without improvement. She then developed rapidly progressive cranial, bulbar, and proximal limb muscle weakness with respiratory distress. Upon admission, she was intubated and found to have a 25% cardiac ejection, but normal coronary arteries by catheterization. Physical examination revealed erythematous patches scattered over the back of her shoulders, upper aspect of her back, thighs, and overlying the joints of the dorsal hands (Fig 1). Neurologic examination showed bilateral facial paresis, ophthalmoplegia, proximal muscle weakness, and areflexia. Initial laboratory testing was significant for an elevated creatine kinase (1178 U/L; normal 25-190 U/L), and aldolase (24 U/L; normal \8.1 U/L). Jo-1, double-stranded DNA, SS-A, SS-B, and Mi-2 antibodies were negative. Nerve conduction studies showed diffusely low compound motor amplitudes with normal velocities, F waves, and latencies. Electromyography showed active myopathy. A skin biopsy specimen of her right shoulder revealed vacuolar interface dermatitis, rare dyskeratotic keratinocytes, and slight increase in dermal mucin, consistent with DM (Fig 2). Biopsy specimen of the biceps muscle was indicative of severe inflammatory myopathy. Initial malignancy workup, including chest, abdomen, and pelvis computed tomography scans and CA125, revealed negative findings. The presence of craniobulbar weakness, areflexia, and low compound motor amplitudes, not usually
Letters e151
Fig 2. Vacuolar interface dermatitis, rare dyskeratotic keratinocytes, and slight increase in dermal mucin. (Hematoxylin-eosin stain.) The authors acknowledge Aleador Andea, MD, for the photomicrograph.
found in DM, suggested a concomitant neuromuscular junction disorder. This possibility was supported by serologic identification of P/Q-type voltage-gated calcium channel antibodies (0.15 nmol/L; normal \0.02 nmol/L), acetylcholine receptor binding antibodies (0.17 nmol/L; normal \0.02 nmol/L), and acetylcholine receptor modulating antibodies (42% loss of acetylcholine receptor; normal 0%-20%). Although repetitive nerve stimulation was not performed, the combined clinical and serologic findings were most consistent with OMS. The patient was treated with intravenous immunoglobulin and Solu-Medrol with neurologic improvement. Six months after discharge, she was noted to have an abnormal mammogram and was subsequently diagnosed with invasive ductal breast carcinoma. To our knowledge, this is the first report of an association between DM and OMS. Both diseases are autoimmune in origin, and have identifiable autoantibodies, although testing for the anti155/140 and anti-CADM-140 antibodies of DM3 were not performed on this patient. Both diseases may also be paraneoplastic in nature. The most common underlying malignancies in DM are colon, ovarian, breast, gastric, or lymphoma,4 with breast, uterine, and ovarian cancer in women being overrepresented in previous reports.5 OMS has previously been associated with small-cell lung cancer6 but not with breast cancer. The rash, proximal muscle weakness, respiratory failure, ophthalmoplegia, and areflexia produced an unusual and diagnostically challenging picture in this acutely ill patient. Dermatologists and neurologists should be aware of the coexistence of these treatable paraneoplastic disorders. Erika K. Hill, MD,a Peter H. King, MD,b,c and Lauren C. Hughey, MDa
J AM ACAD DERMATOL
e152 Letters
NOVEMBER 2011
Departments of Dermatologya and Neurology,b University of Alabama at Birmingham; and Birmingham Veterans Affairs Medical Centerc Funding sources: None. Conflicts of interest: None declared. Correspondence to: Lauren C. Hughey, MD, Department of Dermatology, University of Alabama at Birmingham, 1530 Third Ave S, EFH 414, Birmingham, AL 35294 E-mail: [email protected] REFERENCES 1. Newsom-Davis J, Leys K, Vincent A, Ferguson I, Modi G, Mills K. Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. J Neurol Neurosurg Psychiatry 1991;54: 452-3. 2. Oh SJ, Sher E. MG and LEMS overlap syndrome: case report with electrophysiological and immunological evidence. Clin Neurophysiol 2005;116:1167-71. 3. Hamaguchi Y, Kuwana M, Hoshino K, Hasegawa M, Kaji K, Matsushita T, et al. Clinical correlations with dermatomyositisspecific autoantibodies in adult Japanese patients with dermatomyositis. Arch Dermatol 2011;147:391-8. 4. Hill C, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, et al. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet 2001; 357:96-100. 5. Leandro MJ, Isenberg DA. Rheumatic diseases and malignancyeis there an association? Scand J Rheumatol 2001;30: 185-8. 6. Leger JM, Bachoud-Levi AC, Eymard B, Theodore C, Bouche P, Pierrot-Deseilligny C. Paraneoplastic myasthenic syndrome. Rev Neurol (Paris) 1993;149:485-8. doi:10.1016/j.jaad.2011.07.028
Detection of Merkel cell polyomavirus in cutaneous squamous cell carcinoma before occurrence of Merkel cell carcinoma To the Editor: In 2008, a previously unknown polyomavirus, Merkel cell polyomavirus (MCPyV), was identified in Merkel cell carcinoma (MCC) lesions and close association between MCPyV and MCC has been suggested.1,2 However, to our knowledge, no previous reports have confirmed MCPyV infection in patients with MCC before the occurrence of MCC. We herein report a patient who developed squamous cell carcinoma (SCC) followed by MCC. MCPyV was detected in both tumors by polymerase chain reaction analysis. A 78-year-old Japanese man who had been immunosuppressed as a result of diabetes mellitus noticed a nodule on his right cheek, and the tumor was simply resected (Fig 1, A). The tumor was
Fig 1. Squamous cell carcinoma (SCC) on right cheek (A) and Merkel cell carcinoma (MCC) in left axilla (B). A, Patient presented with crater-shaped nodule on right cheek (arrow). Resected tumor was typical, moderately differentiated SCC. B, Positron emission computed tomography showed solid mass 10 3 30 mm in size in left axilla (white arrow). Histopathologically, lesion was diagnosed as nodal MCC.
diagnosed histopathologically as typical SCC. Coexisting MCC was not found anywhere in the resected specimen by either hematoxylin-eosin stain or immunostaining for cytokeratin 20. One year later, he presented with a subcutaneous nodule in his left axillary lymph node. Positron emission computed tomography showed a solid mass (Fig 1, B). Histopathological, immunohistochemical, and ultrastructural examination revealed that the tumor was a nodal MCC, although the primary lesion was not discovered. Fourteen months after the axillary dissection, he developed multiple metastatic MCC lesions and died 10 months later. The VP1 region of MCPyV DNA was amplified from DNA samples both of the MCC and the SCC lesions (Fig 2, A). Copy numbers of MCPyV DNA large tumor (LT) domain were determined by quantitative real-time polymerase chain reaction using the b-globin gene as an internal control. The MCPyVLT/b-actin in the MCC sample was 3.9 3 104/4.8 3 105 (¼8.1 3 102 copies per cell), and that in the SCC sample was 8.1 3 102/2.0 3 103 (¼4.0 3 103 copies per cell). Larger copy numbers of viral genome were obtained in the MCC lesion. Immunohistochemical staining demonstrated that the MCC cells were