Case report
A case of Marshall’s syndrome and review of the literature 2 € _ Ercan C urol Acßıkg€ oz1, MD, Yıldıray Yeniay1, MD, Ibrahim Ozmen , MD, ß alısßkan1, MD, G€ Mehmet Gamsızkan3, MD, and Ahmet Akar1, MD
1 €lhane Department of Dermatology, Gu €lhane Military School of Medicine, Gu Medical Academy, Ankara, Turkey, 2 Department of Dermatology, C ß orlu Military Hospital, C ß orlu, Turkey, and 3Department of €lhane School of Medicine, Pathology, Gu €lhane Military Medical Academy, Ankara, Gu Turkey
Correspondence Ercan C ß alısßkan, MD Department of Dermatology Gulhane School of Medicine Etlik Kecioren Ankara 06018 Turkey E-mail: [email protected] Conflicts of interest: None.
Cutis laxa (CL) is characterized by the development of loose, wrinkled, and redundant skin as a result of the degradation of elastic fibers in the extracellular matrix.1 This skin disorder may present in an inherited or an acquired form. Previously, the acquired form of CL was subdivided into two groups, respectively, type 1, a generalized acquired elastolysis, and type 2, Marshall’s syndrome. Marshall’s syndrome is characterized by postinflammatory elastolysis associated with various inflammatory dermatoses.2 Herein, we report a rare case of Marshall’s syndrome and review the literature for previously reported cases. Case report A 21-year-old male patient was referred to our clinic for the evaluation of loosening facial skin which had developed slowly over the preceding two years. The subject had a history of asymptomatic erythematous papules on the face and neck, which had spread to the upper extremities and trunk before the progressive wrinkling of his facial skin commenced. He reported that the sagging and wrinkling of his skin had become more pronounced in the one year prior to presentation. His medical history ª 2014 The International Society of Dermatology
included an episode of conjunctivitis that had occurred prior to the onset of these skin lesions. He had no family history of any dermatologic disorders. On physical examination, the patient appeared much older than his actual age as a result of the sagging and wrinkling of his facial skin (Fig. 1a). He had prominent wrinkling on the helix of both ears (Fig. 1b). There was also sagging and wrinkling on the skin of the upper extremities and abdomen, which presented with longitudinal or transverse grooves (Fig. 1c). Close examination of the skin revealed several asymptomatic erythematous papules on the subject’s neck and trunk (Fig. 1d). Skin biopsy specimens were taken from affected skin on the patient’s trunk and from asymptomatic erythematous papules on his neck. On histopathologic examination, the epidermis was found to be unaffected in both specimens. Dermal interstitial neutrophilic infiltration was observed in the papular lesion (Figs. 2 and 3). Verhoeff elastic stain was performed in both specimens and revealed fragmented elastic fibers by neutrophils (Fig. 4). A detailed laboratory examination was conducted for possible etiologic factors. Complete blood count data and routine biochemistry results were within normal limits. Fibrinogen (524 mg/ml [normal range: 200–400 mg/ml]), International Journal of Dermatology 2015, 54, e217–e221
e217
e218
Case report
(a)
C ß alısß kan et al.
Marshall’s syndrome: case report and review
(b)
(c)
(d)
Figure 1 Clinical examination of a 21-year-old man reveals sagging and wrinkling on the patient’s (a) face, (b) ears and (c) abdomen,
where symptoms manifest in transverse grooves. (c) Asymptomatic erythematous papules are located on the patient’s trunk
Figure 2 Histopathology shows a normal epidermis and interstitial infiltration in the dermis. (Hematoxylin and eosin stain; original magnification 9100)
Figure 4 Fragmented elastic fibers and polymorphonuclear leukocytes form a linear configuration around elastic fibers. (Verhoeff elastic stain; original magnification 9400)
Figure 3 Histopathology shows an interstitial neutrophilic infiltration in the dermis. (H&E stain; original magnification 9400)
erythrocyte sedimentation rate (74 mm/h), C-reactive protein (20.8 mg/l [normal range: 0–6 mg/l]), transferrin (413 mg/dl [normal range: 200–360 mg/dl]), and serum copper (148 lg/dl [normal range: 70–140 lg/dl]) levels were found to be elevated. Although the patient’s serum adrenocorticotropic hormone (ACTH) level was elevated (157 pg/ml [normal range: 0–46 pg/ml]), his serum cortisol level was quite normal. Hepatitis B and C markers, antinuclear antibody, and tissue transglutaminase antibodies were negative. Serum alpha-1 antitrypsin level was also found to be within the normal range. Serum immunoglobulin E (IgE) level was high (444.01 IU/ml [normal range: 0–85 IU/ml]), whereas other immunoglobulin levels were within normal limits. Abdominal, thoracic, and pelvic computerized tomography (CT) scans and chest x-ray showed no abnormalities. Pituitary magnetic resonance imaging (MRI) was performed in view of the elevated ACTH levels, and a 5-mm microadenoma was revealed on the left lateral part of the gland. The patient
International Journal of Dermatology 2015, 54, e217–e221
ª 2014 The International Society of Dermatology
C ß alısß kan et al.
Marshall’s syndrome: case report and review
was offered laboratory and radiologic follow-up at the endocrinology clinic. These clinical, laboratory, and radiologic findings led us to confirm the diagnosis of post-inflammatory elastolysis, which is defined as acquired CL type 2 (Marshall’s syndrome). Discussion Cutis laxa is a rare connective tissue disorder, which is characterized by the development of loose, wrinkled, and redundant skin as a result of the degradation of elastic fibers in the extracellular matrix.1 This connective tissue disorder can present in either inherited or acquired forms. Inherited forms include autosomal dominant CL (ADCL), autosomal recessive CL (ARCL), Urban–Rifkin–Davis syndrome (URDS), macrocephaly-alopecia-CL-scoliosis (MACS) syndrome, arterial tortuosity syndrome (ATS), and X-linked CL (XLCL).3 Acquired CL is usually associated with systemic conditions, medications, or inflammatory dermatosis. According to its clinical and histopathologic features, acquired CL is subdivided into two groups representing, respectively, type 1, which is generalized acquired elastolysis, and type 2, or Marshall’s syndrome.2 To date, many etiologic factors associated with acquired CL type 1 have been described, including medications, malignancies, infections, connective tissue diseases, renal diseases, alpha-1 antitrypsin deficiency, mastocytosis, amyloidosis, dermatitis herpetiformis, interstitial granulomatous dermatitis, sarcoidosis, and celiac disease.3,4 Patients are usually adults, and disease usually occurs in the head and neck region and expands peripherally in a craniocaudal fashion with or without preceding inflammatory skin lesions.5,6 Some patients suffer only cutaneous changes, but others may have more widespread diseases with systemic manifestations that include pulmonary emphysema,
Case report
pneumothorax, vascular dilatations, gastrointestinal diverticulae, cor pulmonale, and hernia.3,7 Although most of these conditions result in generalized CL, localized elastolysis may occur in circumscribed conditions such as interstitial granulomatous dermatitis.4 Acquired CL type 2 (Marshall’s syndrome) is usually described as the development of post-inflammatory elastolysis after a Sweet’s syndrome-like neutrophilic dermatosis.8 Whereas some patients have inflammatory lesions that meet the diagnostic criteria for Sweet’s syndrome, others have neutrophilic dermatosis without fever or abnormal laboratory findings.7,9,10 In addition to these distinct clinical features, Marshall’s syndrome associated with Sweet’s syndrome usually presents in childhood and is more common in females.11 By contrast, patients with only neutrophilic dermatosis tend to be older when the skin eruptions manifest.9 The progression of Marshall’s syndrome usually starts in the head and neck region and expands peripherally in a craniocaudal fashion. The course of the disease may be divided into two stages and described as an eruptive phase and an elastolysis phase.7 In the first phase, bright red papules and plaques appear in the head, neck, and upper trunk region and may expand peripherally. The eruptive phase can last for months to years. In some cases, these eruptions may also be observed in the elastolysis phase. In the second phase, skin eruptions begin to fade and clinical signs of postinflammatory elastolysis become evident, especially on the face, giving the subject a blood hound-like appearance. In Marshall’s syndrome, elastolysis is confined to the skin; according to published studies, no systemic involvement has been reported. On histopathologic examination, Marshall’s syndrome consists of two distinct features associated with the stage of disease. Papular lesions in the eruptive phase show no changes in the epidermis. In the dermis, mononuclear
Table 1 Reports of acquired cutis laxa after neutrophilic dermatosis Authors (year)
Preceding dermatosis
Age at onset
Sex
Remarks
Christensen & Gonzalez-Crussi14 Muster et al.15 Chun & Yoon10 Hwang et al.8 Bouloc et al.13 Guia et al.16 Prasad et al.17 Timmer-de Mik et al.18 Haider et al.7 Sun & Chen9 Ma et al.19 This report (2013)
Sweet’s syndrome Sweet’s syndrome Urticarial papules Sweet’s syndrome Urticarial papules Sweet’s syndrome Sweet’s syndrome Sweet’s syndrome Erythematous plaques Urticarial papules Sweet’s syndrome Urticarial papules
17 16 28 16 15 7 1 8 14 15 11 19
F N/A M N/A F M F M F M M M
Aorta were affected Aorta were affected No laboratory abnormalities Alpha-1 antitrypsin deficiency No laboratory abnormalities Aorta were effected Fever and neutrophilia Fever and neutrophilia Fever, neutrophilia, high IgE No laboratory abnormalities Fever and leukocytosis Pituitary microadenoma, high IgE
months months years months years months month months months years years years
F, female; M, male; N/A not available. ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e217–e221
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C ß alısß kan et al.
Marshall’s syndrome: case report and review
inflammatory infiltration is observed around vessels and collagen bundles, along with mild dermal edema. Elastic fibers are markedly thin and fragmented among neutrophilic and eosinophilic infiltration.10 In the elastolysis phase, the epidermis remains preserved. In the dermis, the infiltration of mononuclear cells reduces and elastin fibers diffusely decrease. The remaining elastin fibers become thin and fragmented as a result of previous neutrophilic infiltration. The pathogenesis of acquired CL has not yet been fully elucidated, but according to clinical variants of acquired CL, it is possible that more than one pathogenetic mechanism may be responsible for the progression of disease. It is obvious that the degrading and reduction of elastin fibers represent the basis of the pathogenesis.11 The degradation of elastin fibers is controlled by elastase, which is produced by neutrophils, macrophages, and fibroblasts in the skin and protease inhibitors. High elastase activity was demonstrated in the urticarial papule of a patient with acquired CL.12 In addition, neutrophilic infiltration that causes the fragmenting of elastin fibers was also observed in histopathologic examinations. These data suggest that an unknown factor stimulating elastase activity and/or the dysfunction of elastase/protease inhibitors can result in progressive elastolysis in genetically susceptible individuals. The present report refers to one case of acquired CL after a non-pruritic urticaria-like neutrophilic dermatosis. We searched PubMed for articles on CL and Sweet’s syndrome published from 1980 to 2013 and found reports of 11 cases in which the data available indicated that neutrophilic dermatosis preceded the appearance of acquired CL (Table 1).7–10,13–19 Three cases were associated with urticaria-like neutrophilic dermatosis that preceded the onset of CL, and seven cases were associated with Sweet’s syndrome. Like the previously described cases, our patient had no relevant family history or systemic disease other than pituitary microadenoma, which does not require any treatment. In laboratory examinations, we observed an increase in the concentration of acute-phase reactants, unlike the previously reported cases. As we failed to find any underlying pathology to explain this elevation, we attributed this effect to the widespread involvement of the inflammatory eruptive phase of the disease. Our patient reported a disease duration of two years, whereas patients reported in previous studies cited disease durations of 3–6 years. A high IgE level was the other abnormal laboratory result in our patient. We were unable to identify any reasonable etiologic factor to explain this high IgE level. Although our patient had no history of insect bite, this laboratory result may represent a clue to an idiosyncratic reaction to an International Journal of Dermatology 2015, 54, e217–e221
arthropod bite, which was previously proposed as an etiologic factor for acquired CL.13 In conclusion, acquired CL associated with a Sweet’s syndrome-like neutrophilic infiltration is a rare skin condition that has been observed in adult patients. As far as we know, only three cases have been reported in the previous literature. It is important to emphasize that some of the histopathologic features of this neutrophilic dermatosis are similar to those of Sweet’s syndrome, although no laboratory findings meeting the diagnostic criteria for Sweet’s syndrome were observed. In addition, Marshall’s syndrome has clinically distinct variants according to etiologic factors. Further studies are needed to evaluate the pathogenesis of Marshall’s syndrome, especially in the early phase of the disease. References 1 Mohamed M, Kouwenberg D, Gardeitchik T, et al. Metabolic cutis laxa syndromes. J Inherit Metab Dis 2011; 34: 907–916. 2 Koch SE, Williams ML. Acquired cutis laxa: case report and review of disorders of elastolysis. Pediatr Dermatol 1985; 2: 282–288. 3 Berk DR, Bentley DD, Bayliss SJ, et al. Cutis laxa: a review. J Am Acad Dermatol 2012; 66: e1–e17. 4 Lucas A, Ba~ nuls J, Mataix J, et al. Localized acquired cutis laxa secondary to interstitial granulomatous dermatitis. Clin Exp Dermatol 2009; 34: e102–e105. 5 Gupta A, Helm TN. Acquired cutis laxa associated with multiple myeloma. Cutis 2002; 69: 114–118. 6 Turner RB, Haynes HA, Granter SR, et al. Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma. J Am Acad Dermatol 2009; 60: 1052–1057. 7 Haider M, Alfadley A, Kadry R, et al. Acquired cutis laxa type II (Marshall syndrome) in an 18-month-old child: a case report. Pediatr Dermatol 2010; 27: 89–91. 8 Hwang ST, Williams ML, McCalmont TH, et al. Sweets syndrome leading to acquired cutis laxa (Marshalls syndrome) in an infant with alpha 1-antitrypsin deficiency. Arch Dermatol 1995; 131: 1175–1177. 9 Sun X-K, Chen J-F. No mutation of elastin and fibulin-5 genes in a patient with acquired cutis laxa associated with chronic urticaria. Br J Dermatol 2011; 164: 215–217. 10 Chun SI, Yoon J. Acquired cutis laxa associated with chronic urticaria. J Am Acad Dermatol 1995; 33: 896–899. 11 Verhagen AR, Woerdeman MJ. Post-inflammatory elastolysis and cutis laxa. Br J Dermatol 1975; 92: 183–190. 12 Fornieri C, Quaglino D, Lungarella G, et al. Elastin production and degradation in cutis laxa acquisita. J Invest Dermatol 1994; 103: 583–588. ª 2014 The International Society of Dermatology
C ß alısß kan et al.
13 Bouloc A, Godeau G, Zeller J, et al. Increased fibroblast elastase activity in acquired cutis laxa. Dermatology 1999; 198: 346–350. 14 Christensen CC, Gonzalez-Crussi F. Post-inflammatory elastolysis and cutis laxa: report of a case with aortitis. Pediatr Pathol 1983; 1: 199–210. 15 Muster AJ, Bharati S, Herman JJ, et al. Fatal cardiovascular disease and cutis laxa following acute febrile neutrophilic dermatosis. J Pediatr 1983; 102: 243–248. 16 Guia JM, Frias J, Castro FJ, et al. Cardiovascular involvement in a boy with Sweets syndrome. Pediatr Cardiol 1999; 20: 295–297.
ª 2014 The International Society of Dermatology
Marshall’s syndrome: case report and review
Case report
17 Prasad PVS, Ambujam S, Priya K, et al. Sweets syndrome in an infant – report of a rare case. Int J Dermatol 2002; 41: 928–930. 18 Timmer-de Mik L, Broekhuijsen-van Henten DM, Oldhoff JM, et al. Acquired cutis laxa in childhood Sweets syndrome. Pediatr Dermatol 2009; 26: 358–360. 19 Ma EH, Akikusa JD, MacGregor D, et al. Sweets syndrome with post-inflammatory elastolysis and Takayasu arteritis in a child: a case report and literature review. Pediatr Dermatol 2012; 29: 645–650.
International Journal of Dermatology 2015, 54, e217–e221
e221
A case of Marshall’s syndrome and review of the literature 2 € _ Ercan C urol Acßıkg€ oz1, MD, Yıldıray Yeniay1, MD, Ibrahim Ozmen , MD, ß alısßkan1, MD, G€ Mehmet Gamsızkan3, MD, and Ahmet Akar1, MD
1 €lhane Department of Dermatology, Gu €lhane Military School of Medicine, Gu Medical Academy, Ankara, Turkey, 2 Department of Dermatology, C ß orlu Military Hospital, C ß orlu, Turkey, and 3Department of €lhane School of Medicine, Pathology, Gu €lhane Military Medical Academy, Ankara, Gu Turkey
Correspondence Ercan C ß alısßkan, MD Department of Dermatology Gulhane School of Medicine Etlik Kecioren Ankara 06018 Turkey E-mail: [email protected] Conflicts of interest: None.
Cutis laxa (CL) is characterized by the development of loose, wrinkled, and redundant skin as a result of the degradation of elastic fibers in the extracellular matrix.1 This skin disorder may present in an inherited or an acquired form. Previously, the acquired form of CL was subdivided into two groups, respectively, type 1, a generalized acquired elastolysis, and type 2, Marshall’s syndrome. Marshall’s syndrome is characterized by postinflammatory elastolysis associated with various inflammatory dermatoses.2 Herein, we report a rare case of Marshall’s syndrome and review the literature for previously reported cases. Case report A 21-year-old male patient was referred to our clinic for the evaluation of loosening facial skin which had developed slowly over the preceding two years. The subject had a history of asymptomatic erythematous papules on the face and neck, which had spread to the upper extremities and trunk before the progressive wrinkling of his facial skin commenced. He reported that the sagging and wrinkling of his skin had become more pronounced in the one year prior to presentation. His medical history ª 2014 The International Society of Dermatology
included an episode of conjunctivitis that had occurred prior to the onset of these skin lesions. He had no family history of any dermatologic disorders. On physical examination, the patient appeared much older than his actual age as a result of the sagging and wrinkling of his facial skin (Fig. 1a). He had prominent wrinkling on the helix of both ears (Fig. 1b). There was also sagging and wrinkling on the skin of the upper extremities and abdomen, which presented with longitudinal or transverse grooves (Fig. 1c). Close examination of the skin revealed several asymptomatic erythematous papules on the subject’s neck and trunk (Fig. 1d). Skin biopsy specimens were taken from affected skin on the patient’s trunk and from asymptomatic erythematous papules on his neck. On histopathologic examination, the epidermis was found to be unaffected in both specimens. Dermal interstitial neutrophilic infiltration was observed in the papular lesion (Figs. 2 and 3). Verhoeff elastic stain was performed in both specimens and revealed fragmented elastic fibers by neutrophils (Fig. 4). A detailed laboratory examination was conducted for possible etiologic factors. Complete blood count data and routine biochemistry results were within normal limits. Fibrinogen (524 mg/ml [normal range: 200–400 mg/ml]), International Journal of Dermatology 2015, 54, e217–e221
e217
e218
Case report
(a)
C ß alısß kan et al.
Marshall’s syndrome: case report and review
(b)
(c)
(d)
Figure 1 Clinical examination of a 21-year-old man reveals sagging and wrinkling on the patient’s (a) face, (b) ears and (c) abdomen,
where symptoms manifest in transverse grooves. (c) Asymptomatic erythematous papules are located on the patient’s trunk
Figure 2 Histopathology shows a normal epidermis and interstitial infiltration in the dermis. (Hematoxylin and eosin stain; original magnification 9100)
Figure 4 Fragmented elastic fibers and polymorphonuclear leukocytes form a linear configuration around elastic fibers. (Verhoeff elastic stain; original magnification 9400)
Figure 3 Histopathology shows an interstitial neutrophilic infiltration in the dermis. (H&E stain; original magnification 9400)
erythrocyte sedimentation rate (74 mm/h), C-reactive protein (20.8 mg/l [normal range: 0–6 mg/l]), transferrin (413 mg/dl [normal range: 200–360 mg/dl]), and serum copper (148 lg/dl [normal range: 70–140 lg/dl]) levels were found to be elevated. Although the patient’s serum adrenocorticotropic hormone (ACTH) level was elevated (157 pg/ml [normal range: 0–46 pg/ml]), his serum cortisol level was quite normal. Hepatitis B and C markers, antinuclear antibody, and tissue transglutaminase antibodies were negative. Serum alpha-1 antitrypsin level was also found to be within the normal range. Serum immunoglobulin E (IgE) level was high (444.01 IU/ml [normal range: 0–85 IU/ml]), whereas other immunoglobulin levels were within normal limits. Abdominal, thoracic, and pelvic computerized tomography (CT) scans and chest x-ray showed no abnormalities. Pituitary magnetic resonance imaging (MRI) was performed in view of the elevated ACTH levels, and a 5-mm microadenoma was revealed on the left lateral part of the gland. The patient
International Journal of Dermatology 2015, 54, e217–e221
ª 2014 The International Society of Dermatology
C ß alısß kan et al.
Marshall’s syndrome: case report and review
was offered laboratory and radiologic follow-up at the endocrinology clinic. These clinical, laboratory, and radiologic findings led us to confirm the diagnosis of post-inflammatory elastolysis, which is defined as acquired CL type 2 (Marshall’s syndrome). Discussion Cutis laxa is a rare connective tissue disorder, which is characterized by the development of loose, wrinkled, and redundant skin as a result of the degradation of elastic fibers in the extracellular matrix.1 This connective tissue disorder can present in either inherited or acquired forms. Inherited forms include autosomal dominant CL (ADCL), autosomal recessive CL (ARCL), Urban–Rifkin–Davis syndrome (URDS), macrocephaly-alopecia-CL-scoliosis (MACS) syndrome, arterial tortuosity syndrome (ATS), and X-linked CL (XLCL).3 Acquired CL is usually associated with systemic conditions, medications, or inflammatory dermatosis. According to its clinical and histopathologic features, acquired CL is subdivided into two groups representing, respectively, type 1, which is generalized acquired elastolysis, and type 2, or Marshall’s syndrome.2 To date, many etiologic factors associated with acquired CL type 1 have been described, including medications, malignancies, infections, connective tissue diseases, renal diseases, alpha-1 antitrypsin deficiency, mastocytosis, amyloidosis, dermatitis herpetiformis, interstitial granulomatous dermatitis, sarcoidosis, and celiac disease.3,4 Patients are usually adults, and disease usually occurs in the head and neck region and expands peripherally in a craniocaudal fashion with or without preceding inflammatory skin lesions.5,6 Some patients suffer only cutaneous changes, but others may have more widespread diseases with systemic manifestations that include pulmonary emphysema,
Case report
pneumothorax, vascular dilatations, gastrointestinal diverticulae, cor pulmonale, and hernia.3,7 Although most of these conditions result in generalized CL, localized elastolysis may occur in circumscribed conditions such as interstitial granulomatous dermatitis.4 Acquired CL type 2 (Marshall’s syndrome) is usually described as the development of post-inflammatory elastolysis after a Sweet’s syndrome-like neutrophilic dermatosis.8 Whereas some patients have inflammatory lesions that meet the diagnostic criteria for Sweet’s syndrome, others have neutrophilic dermatosis without fever or abnormal laboratory findings.7,9,10 In addition to these distinct clinical features, Marshall’s syndrome associated with Sweet’s syndrome usually presents in childhood and is more common in females.11 By contrast, patients with only neutrophilic dermatosis tend to be older when the skin eruptions manifest.9 The progression of Marshall’s syndrome usually starts in the head and neck region and expands peripherally in a craniocaudal fashion. The course of the disease may be divided into two stages and described as an eruptive phase and an elastolysis phase.7 In the first phase, bright red papules and plaques appear in the head, neck, and upper trunk region and may expand peripherally. The eruptive phase can last for months to years. In some cases, these eruptions may also be observed in the elastolysis phase. In the second phase, skin eruptions begin to fade and clinical signs of postinflammatory elastolysis become evident, especially on the face, giving the subject a blood hound-like appearance. In Marshall’s syndrome, elastolysis is confined to the skin; according to published studies, no systemic involvement has been reported. On histopathologic examination, Marshall’s syndrome consists of two distinct features associated with the stage of disease. Papular lesions in the eruptive phase show no changes in the epidermis. In the dermis, mononuclear
Table 1 Reports of acquired cutis laxa after neutrophilic dermatosis Authors (year)
Preceding dermatosis
Age at onset
Sex
Remarks
Christensen & Gonzalez-Crussi14 Muster et al.15 Chun & Yoon10 Hwang et al.8 Bouloc et al.13 Guia et al.16 Prasad et al.17 Timmer-de Mik et al.18 Haider et al.7 Sun & Chen9 Ma et al.19 This report (2013)
Sweet’s syndrome Sweet’s syndrome Urticarial papules Sweet’s syndrome Urticarial papules Sweet’s syndrome Sweet’s syndrome Sweet’s syndrome Erythematous plaques Urticarial papules Sweet’s syndrome Urticarial papules
17 16 28 16 15 7 1 8 14 15 11 19
F N/A M N/A F M F M F M M M
Aorta were affected Aorta were affected No laboratory abnormalities Alpha-1 antitrypsin deficiency No laboratory abnormalities Aorta were effected Fever and neutrophilia Fever and neutrophilia Fever, neutrophilia, high IgE No laboratory abnormalities Fever and leukocytosis Pituitary microadenoma, high IgE
months months years months years months month months months years years years
F, female; M, male; N/A not available. ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e217–e221
e219
e220
Case report
C ß alısß kan et al.
Marshall’s syndrome: case report and review
inflammatory infiltration is observed around vessels and collagen bundles, along with mild dermal edema. Elastic fibers are markedly thin and fragmented among neutrophilic and eosinophilic infiltration.10 In the elastolysis phase, the epidermis remains preserved. In the dermis, the infiltration of mononuclear cells reduces and elastin fibers diffusely decrease. The remaining elastin fibers become thin and fragmented as a result of previous neutrophilic infiltration. The pathogenesis of acquired CL has not yet been fully elucidated, but according to clinical variants of acquired CL, it is possible that more than one pathogenetic mechanism may be responsible for the progression of disease. It is obvious that the degrading and reduction of elastin fibers represent the basis of the pathogenesis.11 The degradation of elastin fibers is controlled by elastase, which is produced by neutrophils, macrophages, and fibroblasts in the skin and protease inhibitors. High elastase activity was demonstrated in the urticarial papule of a patient with acquired CL.12 In addition, neutrophilic infiltration that causes the fragmenting of elastin fibers was also observed in histopathologic examinations. These data suggest that an unknown factor stimulating elastase activity and/or the dysfunction of elastase/protease inhibitors can result in progressive elastolysis in genetically susceptible individuals. The present report refers to one case of acquired CL after a non-pruritic urticaria-like neutrophilic dermatosis. We searched PubMed for articles on CL and Sweet’s syndrome published from 1980 to 2013 and found reports of 11 cases in which the data available indicated that neutrophilic dermatosis preceded the appearance of acquired CL (Table 1).7–10,13–19 Three cases were associated with urticaria-like neutrophilic dermatosis that preceded the onset of CL, and seven cases were associated with Sweet’s syndrome. Like the previously described cases, our patient had no relevant family history or systemic disease other than pituitary microadenoma, which does not require any treatment. In laboratory examinations, we observed an increase in the concentration of acute-phase reactants, unlike the previously reported cases. As we failed to find any underlying pathology to explain this elevation, we attributed this effect to the widespread involvement of the inflammatory eruptive phase of the disease. Our patient reported a disease duration of two years, whereas patients reported in previous studies cited disease durations of 3–6 years. A high IgE level was the other abnormal laboratory result in our patient. We were unable to identify any reasonable etiologic factor to explain this high IgE level. Although our patient had no history of insect bite, this laboratory result may represent a clue to an idiosyncratic reaction to an International Journal of Dermatology 2015, 54, e217–e221
arthropod bite, which was previously proposed as an etiologic factor for acquired CL.13 In conclusion, acquired CL associated with a Sweet’s syndrome-like neutrophilic infiltration is a rare skin condition that has been observed in adult patients. As far as we know, only three cases have been reported in the previous literature. It is important to emphasize that some of the histopathologic features of this neutrophilic dermatosis are similar to those of Sweet’s syndrome, although no laboratory findings meeting the diagnostic criteria for Sweet’s syndrome were observed. In addition, Marshall’s syndrome has clinically distinct variants according to etiologic factors. Further studies are needed to evaluate the pathogenesis of Marshall’s syndrome, especially in the early phase of the disease. References 1 Mohamed M, Kouwenberg D, Gardeitchik T, et al. Metabolic cutis laxa syndromes. J Inherit Metab Dis 2011; 34: 907–916. 2 Koch SE, Williams ML. Acquired cutis laxa: case report and review of disorders of elastolysis. Pediatr Dermatol 1985; 2: 282–288. 3 Berk DR, Bentley DD, Bayliss SJ, et al. Cutis laxa: a review. J Am Acad Dermatol 2012; 66: e1–e17. 4 Lucas A, Ba~ nuls J, Mataix J, et al. Localized acquired cutis laxa secondary to interstitial granulomatous dermatitis. Clin Exp Dermatol 2009; 34: e102–e105. 5 Gupta A, Helm TN. Acquired cutis laxa associated with multiple myeloma. Cutis 2002; 69: 114–118. 6 Turner RB, Haynes HA, Granter SR, et al. Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma. J Am Acad Dermatol 2009; 60: 1052–1057. 7 Haider M, Alfadley A, Kadry R, et al. Acquired cutis laxa type II (Marshall syndrome) in an 18-month-old child: a case report. Pediatr Dermatol 2010; 27: 89–91. 8 Hwang ST, Williams ML, McCalmont TH, et al. Sweets syndrome leading to acquired cutis laxa (Marshalls syndrome) in an infant with alpha 1-antitrypsin deficiency. Arch Dermatol 1995; 131: 1175–1177. 9 Sun X-K, Chen J-F. No mutation of elastin and fibulin-5 genes in a patient with acquired cutis laxa associated with chronic urticaria. Br J Dermatol 2011; 164: 215–217. 10 Chun SI, Yoon J. Acquired cutis laxa associated with chronic urticaria. J Am Acad Dermatol 1995; 33: 896–899. 11 Verhagen AR, Woerdeman MJ. Post-inflammatory elastolysis and cutis laxa. Br J Dermatol 1975; 92: 183–190. 12 Fornieri C, Quaglino D, Lungarella G, et al. Elastin production and degradation in cutis laxa acquisita. J Invest Dermatol 1994; 103: 583–588. ª 2014 The International Society of Dermatology
C ß alısß kan et al.
13 Bouloc A, Godeau G, Zeller J, et al. Increased fibroblast elastase activity in acquired cutis laxa. Dermatology 1999; 198: 346–350. 14 Christensen CC, Gonzalez-Crussi F. Post-inflammatory elastolysis and cutis laxa: report of a case with aortitis. Pediatr Pathol 1983; 1: 199–210. 15 Muster AJ, Bharati S, Herman JJ, et al. Fatal cardiovascular disease and cutis laxa following acute febrile neutrophilic dermatosis. J Pediatr 1983; 102: 243–248. 16 Guia JM, Frias J, Castro FJ, et al. Cardiovascular involvement in a boy with Sweets syndrome. Pediatr Cardiol 1999; 20: 295–297.
ª 2014 The International Society of Dermatology
Marshall’s syndrome: case report and review
Case report
17 Prasad PVS, Ambujam S, Priya K, et al. Sweets syndrome in an infant – report of a rare case. Int J Dermatol 2002; 41: 928–930. 18 Timmer-de Mik L, Broekhuijsen-van Henten DM, Oldhoff JM, et al. Acquired cutis laxa in childhood Sweets syndrome. Pediatr Dermatol 2009; 26: 358–360. 19 Ma EH, Akikusa JD, MacGregor D, et al. Sweets syndrome with post-inflammatory elastolysis and Takayasu arteritis in a child: a case report and literature review. Pediatr Dermatol 2012; 29: 645–650.
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