- Email: [email protected]
Diagnosis of linear IgA disease: The results of immunopathologic examinations can be ambiguous
LETTERS NOTES
& COMMENTS
Mucous membrane pemphigoid: Do we really care about a more specific diagnosis? To the Editor: I was puzzled to read the recent contribution by Dan et al,1 who reported an alleged case of linear immunoglobulin (Ig) A disease (LAD) confined to the gingival mucosa as the data provided are not enough to establish a diagnosis. In fact, the junctional linear deposition of IgA may also be found in other subepithelial autoimmune bullous disorders, that is, cicatricial pemphigoid and epidermolysis bullosa acquisita, in which an (exclusive) mucosal involvement is far more common than in LAD.2 Under a practical point of view, though, one may also wonder what the real usefulness is of distinguishing between the various subepithelial autoimmune bullous disorders affecting the mucous membranes, as management is basically left to the physician’s discretion in the lack of strong evidencebased data for the diagnosis and treatment of these conditions. According to an international consensus,3 maybe it is easier to label every case characterized by predominant mucosal involvement and linear deposition of Ig or C3 along the basement membrane zone as ‘‘mucous membrane pemphigoid’’ regardless of the immunoglobulin isotype and target autoantigen(s). Daniele Torchia, MD, PhD Private practice, Florence Funding sources: None. Conflicts of interest: None declared. Correspondence to: Daniele Torchia, MD, PhD, Via della Scala 58, 50123 Florence, Italy E-mail: [email protected]
REFERENCES 1. Dan H, Lu R, Li W, Chen Q, Zeng X. Linear IgA disease limited to the oral mucosa. J Am Acad Dermatol 2011;65:677-9. 2. Torchia D, Caproni M, Fabbri P. Linear IgA disease and desquamative gingivitis: time for inclusion in mucous membrane pemphigoid. Oral Dis 2008;14:768-9. 3. Chan LS, Razzaque Ahmed A, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. The first international consensus on mucous membrane pemphigoid. Definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic factors. Arch Dermatol 2002;138:370-9. doi:10.1016/j.jaad.2011.11.968
156
JULY 2012
Diagnosis of linear IgA disease: The results of immunopathologic examinations can be ambiguous To the Editor: We would like to take this opportunity to thank Dr Torchia for her comments on our published paper.1 And here is our response to the points raised. Direct immunofluorescence (DIF) on fresh tissue is the ‘‘gold standard’’ for diagnosis of linear immunoglobulin (Ig) A disease. We agreed that other immunopathologic examinations might help to verify the diagnosis; however, sometimes the results of these tests can be ambiguous as well. For example, the IgA autoantibodies tend to bind to the epithelial side of the salt-split skin in most cases; however, they can also bind to the dermal side, which makes it difficult to distinguish them from cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA). Similar results can also be obtained from an immunoblotting test, as the autoantibodies of LAD sera not only recognize 97 kd (LABD97) or 120 kd (LAD-1) antigens but also antigens such as 180 kd (BPAg2), 230 kd (BPAg1), and 290 kd (type VII collagen) antigens. The last 3 antigens are also shared by other subepithelial autoimmune bullous diseases (SABD), such as bullous pemphigoid (BP), CP, and EBA.2 The mechanism of different immunoglobulin isotypes in the pathogenesis of SABD has not been well elucidated. It is possible that they may play different roles in these diseases and drugs targeting different immunoglobulin autoantibodies may be applied in the treatment of SABD in the future. So we think it’s still useful to distinguish between different types of SABD. Xin Jin, PhD, DDS, Lili Wang, PhD, DDS, Xin Zeng, PhD, DDS, and Hongxia Dan, PhD, DDS State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University Funding sources: The National Natural Science Foundation of China (No. 30930100, 81072218) and the Science Funds for Talented Professionals of Sichuan Province in China (No. 09ZQ026-037). Conflicts of interest: None declared. Correspondence to: Hongxia Dan, PhD, DDS, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University. J AM ACAD DERMATOL
J AM ACAD DERMATOL
Letters 157
VOLUME 67, NUMBER 1
No.14, Sec 3, Renminnan Road, Chengdu, Sichuan 610041, China E-mail: [email protected] REFERENCES 1. Dan H, Lu R, Li W, Chen Q, Zeng X. Linear IgA disease limited to the oral mucosa. J Am Acad Dermatol 2011;65:677-9. 2. Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012;30:38-50. doi:10.1016/j.jaad.2012.02.040
Application of in vivo reflectance confocal microscopy in melasma classification To the Editor: Dr Sheth and Pandya’s CME (October 2011) addressed the important issue of classification of melasma according to the depth of melanin.1 Traditionally, melasma has been classified as epidermal, dermal, and mixed type on the basis of Wood light examination. However, current studies have suggested Wood light examination may not be accurate to determine the depth of pigment.2,3 There was a poor correlation between classification based on Wood light examination and histopathology, with apparent epidermal melasma after a Wood lamp examination having significant melanin in the dermis on histopathology.2,3 In vivo reflectance confocal microscopy (RCM) can now challenge skin biopsy specimens in evaluation of pigmentary changes in melasma at a cellular level resolution.4-6 Based on the RCM images, melasma is classified into two major types: epidermal and mixed, which showed complete coherence with histopathology results.4,5 The inconsistency between Wood’s lamp and RCM in classification was shown. For example, a case classified as the dermal type, according to Wood’s lamp test, showed a prominent amount of epidermal pigment but less in the dermis upon RCM examination.6 Moreover, RCM provides a potential advantage over biopsy specimens as the entire lesion can be analyzed in vivo. When the entire melasma lesion was examined, RCM showed that the topographic distribution of melanophages was very heterogeneous within and among different regions.4 These findings suggested that a reliable classification should be based on the ratio of epidermal to dermal melanin involving the whole lesional skin. Finally, RCM analysis of pigmentation can help monitor the response to therapy.6 Therefore, RCM may provide an innovative, noninvasive way to classify melasma. It would be interesting in future clinical studies to study whether the type of melasma as determined by RCM correlates with treatment outcome.
Hee Young Kang, MD, PhD,a and Philippe Bahadoran, MD, PhDb Departments of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea,a and Archet-2 Hospital, Nice, Franceb Funding sources: None. Conflicts of interest: None declared. Correspondence to: Philippe Bahadoran, MD, PhD, Department of Dermatology, Archet-2 Hospital, 151 Route St Antoine de Ginestiere, BP 3079, 06202 Nice Cedex 3, France E-mail: [email protected] REFERENCES 1. Sheth VM, Pandya AG. Melasma: A comprehensive update. Part I. J Am Acad Dermatol 2011;65:689-97. 2. Grimes PE, Yamada N, Bhawan J. Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma. Am J Dermatopathol 2005;27:96-101. 3. Sarvjot V, Sharma S, Mishra S, Singh A. Melasma: a clinicopathological study of 43 cases. Indian J Pathol Microbiol 2009;52:357-9. 4. Kang HY, Bahadoran P, Suzuki I, Zugaj D, Khemis A, Passeron T, et al. In vivo reflectance confocal microscopy detects pigmentary changes in melasma at a cellular level resolution. Exp Dermatol 2010;19:e228-33. 5. Liu H, Lin Y, Nie X, Chen S, Chen X, Shi B, et al. Histological classification of melasma with reflectance confocal microscopy: a pilot study in Chinese patients. Skin Res Technol 2011;17:398-403. 6. Ardigo M, Cameli N, Berardesca E, Gonzalez S. Characterization and evaluation of pigment distribution and response to therapy in melasma using in vivo reflectance confocal microscopy: a preliminary study. J Eur Acad Dermatol Venereol 2010;24:1296-303. doi:10.1016/j.jaad.2012.02.046
Reply To the Editor: We would like to thank the authors for pointing out reflectance confocal microscopy (RCM) as a new technology that might be useful in the evaluation of melasma. The noninvasive nature of this technique has great potential for better understanding melasma and response to treatment. The authors cited two studies with small groups of patients comparing RCM to biopsy specimens from patients with melasma and showing good correlation between histologic findings and RCM findings. Further, larger studies with blinded evaluators and patients of different skin types and races are needed to confirm these findings. Like dermatoscopy in its infancy, the descriptive terms used with RCM will need to be refined and agreed upon by a wider audience so that phrases like ‘‘strongly visible papillary rings,’’ ‘‘fuzzy round or polygonal refractile structures,’’ and ‘‘hyperrefractile cobblestone pattern’’
& COMMENTS
Mucous membrane pemphigoid: Do we really care about a more specific diagnosis? To the Editor: I was puzzled to read the recent contribution by Dan et al,1 who reported an alleged case of linear immunoglobulin (Ig) A disease (LAD) confined to the gingival mucosa as the data provided are not enough to establish a diagnosis. In fact, the junctional linear deposition of IgA may also be found in other subepithelial autoimmune bullous disorders, that is, cicatricial pemphigoid and epidermolysis bullosa acquisita, in which an (exclusive) mucosal involvement is far more common than in LAD.2 Under a practical point of view, though, one may also wonder what the real usefulness is of distinguishing between the various subepithelial autoimmune bullous disorders affecting the mucous membranes, as management is basically left to the physician’s discretion in the lack of strong evidencebased data for the diagnosis and treatment of these conditions. According to an international consensus,3 maybe it is easier to label every case characterized by predominant mucosal involvement and linear deposition of Ig or C3 along the basement membrane zone as ‘‘mucous membrane pemphigoid’’ regardless of the immunoglobulin isotype and target autoantigen(s). Daniele Torchia, MD, PhD Private practice, Florence Funding sources: None. Conflicts of interest: None declared. Correspondence to: Daniele Torchia, MD, PhD, Via della Scala 58, 50123 Florence, Italy E-mail: [email protected]
REFERENCES 1. Dan H, Lu R, Li W, Chen Q, Zeng X. Linear IgA disease limited to the oral mucosa. J Am Acad Dermatol 2011;65:677-9. 2. Torchia D, Caproni M, Fabbri P. Linear IgA disease and desquamative gingivitis: time for inclusion in mucous membrane pemphigoid. Oral Dis 2008;14:768-9. 3. Chan LS, Razzaque Ahmed A, Anhalt GJ, Bernauer W, Cooper KD, Elder MJ, et al. The first international consensus on mucous membrane pemphigoid. Definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic factors. Arch Dermatol 2002;138:370-9. doi:10.1016/j.jaad.2011.11.968
156
JULY 2012
Diagnosis of linear IgA disease: The results of immunopathologic examinations can be ambiguous To the Editor: We would like to take this opportunity to thank Dr Torchia for her comments on our published paper.1 And here is our response to the points raised. Direct immunofluorescence (DIF) on fresh tissue is the ‘‘gold standard’’ for diagnosis of linear immunoglobulin (Ig) A disease. We agreed that other immunopathologic examinations might help to verify the diagnosis; however, sometimes the results of these tests can be ambiguous as well. For example, the IgA autoantibodies tend to bind to the epithelial side of the salt-split skin in most cases; however, they can also bind to the dermal side, which makes it difficult to distinguish them from cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA). Similar results can also be obtained from an immunoblotting test, as the autoantibodies of LAD sera not only recognize 97 kd (LABD97) or 120 kd (LAD-1) antigens but also antigens such as 180 kd (BPAg2), 230 kd (BPAg1), and 290 kd (type VII collagen) antigens. The last 3 antigens are also shared by other subepithelial autoimmune bullous diseases (SABD), such as bullous pemphigoid (BP), CP, and EBA.2 The mechanism of different immunoglobulin isotypes in the pathogenesis of SABD has not been well elucidated. It is possible that they may play different roles in these diseases and drugs targeting different immunoglobulin autoantibodies may be applied in the treatment of SABD in the future. So we think it’s still useful to distinguish between different types of SABD. Xin Jin, PhD, DDS, Lili Wang, PhD, DDS, Xin Zeng, PhD, DDS, and Hongxia Dan, PhD, DDS State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University Funding sources: The National Natural Science Foundation of China (No. 30930100, 81072218) and the Science Funds for Talented Professionals of Sichuan Province in China (No. 09ZQ026-037). Conflicts of interest: None declared. Correspondence to: Hongxia Dan, PhD, DDS, State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University. J AM ACAD DERMATOL
J AM ACAD DERMATOL
Letters 157
VOLUME 67, NUMBER 1
No.14, Sec 3, Renminnan Road, Chengdu, Sichuan 610041, China E-mail: [email protected] REFERENCES 1. Dan H, Lu R, Li W, Chen Q, Zeng X. Linear IgA disease limited to the oral mucosa. J Am Acad Dermatol 2011;65:677-9. 2. Fortuna G, Marinkovich MP. Linear immunoglobulin A bullous dermatosis. Clin Dermatol 2012;30:38-50. doi:10.1016/j.jaad.2012.02.040
Application of in vivo reflectance confocal microscopy in melasma classification To the Editor: Dr Sheth and Pandya’s CME (October 2011) addressed the important issue of classification of melasma according to the depth of melanin.1 Traditionally, melasma has been classified as epidermal, dermal, and mixed type on the basis of Wood light examination. However, current studies have suggested Wood light examination may not be accurate to determine the depth of pigment.2,3 There was a poor correlation between classification based on Wood light examination and histopathology, with apparent epidermal melasma after a Wood lamp examination having significant melanin in the dermis on histopathology.2,3 In vivo reflectance confocal microscopy (RCM) can now challenge skin biopsy specimens in evaluation of pigmentary changes in melasma at a cellular level resolution.4-6 Based on the RCM images, melasma is classified into two major types: epidermal and mixed, which showed complete coherence with histopathology results.4,5 The inconsistency between Wood’s lamp and RCM in classification was shown. For example, a case classified as the dermal type, according to Wood’s lamp test, showed a prominent amount of epidermal pigment but less in the dermis upon RCM examination.6 Moreover, RCM provides a potential advantage over biopsy specimens as the entire lesion can be analyzed in vivo. When the entire melasma lesion was examined, RCM showed that the topographic distribution of melanophages was very heterogeneous within and among different regions.4 These findings suggested that a reliable classification should be based on the ratio of epidermal to dermal melanin involving the whole lesional skin. Finally, RCM analysis of pigmentation can help monitor the response to therapy.6 Therefore, RCM may provide an innovative, noninvasive way to classify melasma. It would be interesting in future clinical studies to study whether the type of melasma as determined by RCM correlates with treatment outcome.
Hee Young Kang, MD, PhD,a and Philippe Bahadoran, MD, PhDb Departments of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea,a and Archet-2 Hospital, Nice, Franceb Funding sources: None. Conflicts of interest: None declared. Correspondence to: Philippe Bahadoran, MD, PhD, Department of Dermatology, Archet-2 Hospital, 151 Route St Antoine de Ginestiere, BP 3079, 06202 Nice Cedex 3, France E-mail: [email protected] REFERENCES 1. Sheth VM, Pandya AG. Melasma: A comprehensive update. Part I. J Am Acad Dermatol 2011;65:689-97. 2. Grimes PE, Yamada N, Bhawan J. Light microscopic, immunohistochemical, and ultrastructural alterations in patients with melasma. Am J Dermatopathol 2005;27:96-101. 3. Sarvjot V, Sharma S, Mishra S, Singh A. Melasma: a clinicopathological study of 43 cases. Indian J Pathol Microbiol 2009;52:357-9. 4. Kang HY, Bahadoran P, Suzuki I, Zugaj D, Khemis A, Passeron T, et al. In vivo reflectance confocal microscopy detects pigmentary changes in melasma at a cellular level resolution. Exp Dermatol 2010;19:e228-33. 5. Liu H, Lin Y, Nie X, Chen S, Chen X, Shi B, et al. Histological classification of melasma with reflectance confocal microscopy: a pilot study in Chinese patients. Skin Res Technol 2011;17:398-403. 6. Ardigo M, Cameli N, Berardesca E, Gonzalez S. Characterization and evaluation of pigment distribution and response to therapy in melasma using in vivo reflectance confocal microscopy: a preliminary study. J Eur Acad Dermatol Venereol 2010;24:1296-303. doi:10.1016/j.jaad.2012.02.046
Reply To the Editor: We would like to thank the authors for pointing out reflectance confocal microscopy (RCM) as a new technology that might be useful in the evaluation of melasma. The noninvasive nature of this technique has great potential for better understanding melasma and response to treatment. The authors cited two studies with small groups of patients comparing RCM to biopsy specimens from patients with melasma and showing good correlation between histologic findings and RCM findings. Further, larger studies with blinded evaluators and patients of different skin types and races are needed to confirm these findings. Like dermatoscopy in its infancy, the descriptive terms used with RCM will need to be refined and agreed upon by a wider audience so that phrases like ‘‘strongly visible papillary rings,’’ ‘‘fuzzy round or polygonal refractile structures,’’ and ‘‘hyperrefractile cobblestone pattern’’