Dermatomyositis of Wong: A Rare Dermatomyositis Variant
Dermatomyositis (DM) is an inflammatory myopathy with prototypic and characteristic skin lesions: the often subtle heliotrope rash, a violaceous or hypopigmented papule over the joints of the fingers, erythema of the upper back (the Gottron’s papule), extensive erythema of the extensor surfaces of the arms, scaly alopecia and cuticular overgrowth with periungual telangiectasias.1-3 Myopathic DM is defined by the criteria listed in the Table.4,5
Although myositis usually eventuates, skin involvement may be unaccompanied initially by objective evidence of muscle disease; such cases are referred to as amyopathic DM or DM sine myositis.6 In adult populations, roughly one-third of patients have an underlying malignancy, with statistical correlation demonstrated to lymphoma and to carcinomas of ovary, lung, pancreas, colon and stomach.2,7 Other manifestations include arthritis, myocarditis and esophageal and pulmonary disease. DM appears to represent an aberrant immune response directed principally at endothelia in an immunogenetically predisposed individual following antigenic stimuli such as neoplasms, drugs or infections. With respect to the latter, it has been demonstrated that symptomatology in some cases of DM reflect the presence of endotheliotropic viruses such as Parvovirus B19 that may alter endothelial antigenicity.8,9
The pathogenetic basis of the vascular changes is one reflective of antibodies to endothelium. Perhaps, corroborative serologically is the presence of elevated factor VIII levels in patients with active disease, as well almost all patients with DM will have positive indirect immunofluorescent studies in regards to anti-endothelial cell antibodies and exhibit a very distinctive Western blot profile. Concerning the latter, the patient’s serum is typically reactive to multiple protein targets.
A distinctive rare variant of DM is an erythrodermic subtype exhibiting concomitant clinical and histological changes of pityriasis rubra pilaris (PRP), the so-called Wong type DM. It bears this designation to reflect the physician who first described this entity in 1969.The essence of DM of Wong is generalized erythematous and hyperkeratotic cutaneous lesions that resemble PRP in patients who otherwise have typical features of DM be it in the context of myopathic and or amyopathic DM.10
A review of the literature describes an “erythrodermic variant of DM” including 2 cases of juvenile DM in younger patients without using the specific designation of DM of Wong. However, whether this erythrodermic presentation of DM was associated with other diagnostic features of PRP in the few reported cases is not known.11-17
Here, we describe an additional case of erythrodermic DM, which we feel is best categorized as DM of Wong. The case was a diagnostic puzzle until a biopsy was performed demonstrating features, which we hold to be characteristic of DM of Wong.
An 89-year-old female with a history significant for chronic myelogenous leukemia (CML) in remission and on imatinib mesylate therapy (Gleevec, Novartis) for 1 year presented with a diffuse rash described as psoriasiform papules coalescing into plaques involving the trunk, arms and thighs (Figure 1A-B). Presumed to be a psoriasiform drug eruption, imatinib mesylate was discontinued and the patient was treated with prednisone and topical steroid therapy. However, the rash progressed within the next few months to erythroderma with scaling. Other medications, which were initiated to counteract the effects of imatinib mesylate therapy including omeprazole, lomotil and compazine were discontinued without effect. Skip areas, scalp involvement and palmar plaques were noted and clinically consonant with a diagnosis of PRP. In addition, the patient had a distinct heliotrope rash on her eyes highly reminiscent of DM (Figure 1C).
Figure 1A-C. The patient presents with significant erythroderma and also has a keratoderma. She had a distinct heliotrope (not illustrated).
Multiple biopsies were performed all revealing a similar process. In particular, the epidermis ranges in quality from slight hyperplasia to zones of significant attenuation. A distinctive feature was the presence of ichthyotic-like orthohyperkeratosis with focal parakeratosis typical of PRP (Figure 2).
Figure 2. The epidermis shows a psoriasiform epidermal hyperplasia with adjacent areas of attenuation. Ichthyotic-like orthohyperkeratosis with focal parakeratosis typical of pityriasis rubia pilaris is noted.
Also characteristic for PRP was the quality of the granular cell layer; in particular it was increased with large and irregular keratohyalin granules peripherally disposed within the keratinocytes. However, there were other morphologic alterations typical of DM including a cell poor interface dermatitis along with epidermal attenuation. In addition, distinct alterations of the superficial vascular plexus typical of DM were noted and included superficial vascular ectasia with focal endothelial cell detachment (Figure 3).
Figure 3. Cell poor interface dermatitis along with epidermal attenuation is seen. Distinct alterations of the superficial vascular plexus typical of dermatomyositis including superficial vascular ectasia with focal endothelial cell detachment are noted.
Interstitial and perivascular mucin deposition was also identified within the dermis, a finding corroborative of a connective tissue disease diathesis (Figure 4A).
Figure 4. A. Hematoxylin and esosin sections show interstitial and perivascular mucin deposition within the dermis.
An Alcian blue preparation confirmed the presence of extensive mucin deposition within the dermis (Figure 4B); however, the periodic acid-Schiff stain did not show any significant epidermal basement membrane zone reduplication.
Figure 4B. An Alcian blue preparation confirmed the presence of abundant mucin.
Immunohistochemical stains revealed weak endothelial cell staining for myxovirus protein (MxA) (Figure 5A-B), a type 1 interferon microenvironment surrogate marker, and prominent deposits of C5b-9 within the cutaneous vasculature in the mid and deeper dermis (Figure 6). Both findings are characteristic of DM and point toward a role of immune-based microvascular injury.
Figure 5A-B. Immunohistochemical stains reveals weak endothelial cell staining for myxovirus protein, a type 1 interferon microenvironment surrogate marker.
Figure 6. Prominent deposits of C5b-9 are noted within the cutaneous vasculature in the mid and deeper dermis (arrow).
Our patient presented with progressive erythroderma and a history of CML. Skin biopsies showed a very unusual presentation of a mixed DM and PRP defining the essence of so-called Wong type DM.
In 1956, Brunsting et al reviewed the records of 270 patients with DM at the Mayo Clinic and reported 2 cases that had generalized erythematous eruptions simulating PRP consisting of areas of hyperkeratosis and hyperpigmentation before the onset of the typical signs and symptoms of DM. One year later, the patients developed symptoms and signs characteristic of DM with confirmatory muscle biopsy and electromyographic studies in 1 patient and rapid death due to obstructive bronchial aspiration secondary to DM in the second patient.18
In 1969, Wong described this distinctive cutaneous eruption characterized by a PRP-like morphology in 11 patients from a total of 23 patients with DM in Hong Kong.10 In all cases, the patient had DM-like features clinically including in the context of the characteristic heliotrope rash and Gottron’s papules with or without myositis. However, there was supervening erythroderma whereby the erythrodermic presentation was reminiscent of PRP by virtue of follicular hyperkeratotic papules and islands of spared skin, as well a perceptible increase of local temperature was noted in areas of skin involvement. Histopathological examination demonstrated a hybrid morphology analogous to the changes present in this biopsy. In particular, biopsies showed combined features of PRP with other features typical of DM. In these earlier articles, the authors emphasized the interface dermatitis component with mucin deposition as those features typical of DM, although specific reference to the characteristic microvascular changes of DM was not made.
The vast majority of DM cases show the characteristic microvascular changes indicative of an antiendothelial antibody mediated-microangiopathy where they are most conspicuous within the superficially disposed vessels. They comprise mural and luminal fibrin deposition with variable endothelial cell necrosis. As sequelae of the endothelial-based injury, there are concomitant chronic vascular changes namely those of vascular ectasia and vascular drop out. Our case of DM of Wong showed microvascular alterations typical of DM. In addition, a cardinal hallmark of DM immunohistochemically is the upregulation of MxA within the microvasculature, a finding demonstrated in this case.
Twenty-three cases of DM of Wong have been reported in the literature. In all of these patients, an erythrodermic presentation with follicular hyperkeratosis typical of PRP were observed in association with DM.19-22 In particular, the DM of Wong has not been associated with internal malignancy at the same frequency as more conventional forms of DM, although it has been suggested that the young age of patients described so far (mean age 36 years) might be relevant.22 In 1 patient, DM of Wong and porokeratosis was observed at the same time. It was postulated that porokeratosis as a sign of immunosuppression could raise the possibility of an underlying malignancy and warrants a complete investigation for such an occult disease.19 There might be an increased risk for myositis as well as interstitial lung disease in patients with DM of Wong including a recent case where the patient had concomitant antibodies to melanoma differentiation-associated gene 5.22
Erythroderma can occur in the setting of DM. It is reasonable to use the designation of erythrodermic DM in cases that do not have characteristic clinical and histologic features of PRP. If the patient exhibits a true hybrid picture clinically and histologically of DM and PRP, then the designation of DM of Wong is most appropriate. The pathogenetic basis of DM of Wong likely reflects the autoimmune endothelialitis that contributes to the DM component of the illness in concert with disturbances in the immune system attributable to the effects of immunosuppressive therapy used to treat DM, associated malignancy and/or intrinsic to DM itself given the known role of an aberrant immune system in the pathogenesis of PRP.
Dr. Magro is the director of dermatopathology at the Weill Cornell Medical College in Manhattan NY, and is board certified in anatomic pathology, dermatopathology and cytopathology.
Dr. Magro is an expert in the diagnosis of complex inflammatory skin diseases. Her areas of expertise include cutaneous manifestations of autoimmune disease, systemic viral disease and vasculitis, atypical drug reactions, benign, atypical and overtly malignant lymphocytic infiltrates of the skin and diagnostically difficult melanocytic proliferations. For more information, please visit www.weillcornelldermpath.com.
Disclosure: The authors report no relevant financial relationships.
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