Case Report: A case of hypertrophic lupus erythematosus with negative CD123 staining and absence of transepidermal elimination of elastin

We report the case of a 49-year-old male with clinical and histological findings consistent with hypertrophic lupus erythematosus (HLE). HLE must be clinically and histologically differentiated from keratoacanthoma, hypertrophic lichen planus, squamous cell carcinoma and plaque type psoriasis. CD123 positivity and transepidermal elimination of elastin have recently been reported as tools to distinguish HLE. Interestingly, in this case, biopsies of two separate lesions failed to reveal these two features. The etiology of this discrepancy is unknown and further studies are needed to clarify the utility of CD123 positivity and transepidermal elimination of elastin in the diagnosis of hypertrophic lupus erythematosus.

Hypertrophic lupus erythematosus (HLE) is a rare subset of discoid lupus erythematosus, characterized by erythematous, indurated, verrucous papules and nodules located on sun-exposed areas.HLE must be clinically and histologically differentiated from keratoacanthoma, hypertrophic lichen planus, squamous cell carcinoma and plaque type psoriasis.CD123 positivity and transepidermal elimination of elastin have recently been reported to distinguish HLE 1,2 .

Report of case
A 49-year-old, unemployed, white male presented with a three-year history of an expanding "rash".He reported no constitutional symptoms.He had previously been treated with oral prednisone and an unknown topical steroid without improvement and was off all medications at our initial visit.The patient had a past medical history of hepatitis C.He denied a family history of skin or autoimmune diseases.Laboratory work-up was significant for positive anti-nuclear antibodies and anti-Ro antibodies.Physical exam revealed multiple hyperkeratotic, verrucous papules and nodules with white, scaly, cribriform centers overlying patches of depigmentation, erythema and atrophy on his bilateral arms (Figure 1) and anterior legs.His face and scalp had several atrophic, depigmented patches.Two punch biopsies were obtained from separate lesions.Histological  sections demonstrated an interface inflammatory pattern with deep peri-vascular and peri-appendageal lymphocytic infiltrate and rare plasma cells (Figure 2).A diagnosis of HLE was made.The patient was prescribed clobetasol ointment 0.05% twice daily.At the three month follow-up, there was improvement of the hypertrophic lesions.
The patient was subsequently lost to follow-up.In this patient, we examined these two recently described histologic features of HLE.Interestingly, both CD123 positivity and transepidermal elimination of elastin were not present in this case (Figure 3).However, the histological and clinical findings were most consistent with HLE.The etiology of this discrepancy is unknown and further studies are needed to clarify the utility of CD123 positivity and transepidermal elimination of elastin in the diagnosis of hypertrophic lupus erythematosus.

Discussion
There is no definitive treatment for HLE.Options include topical or intralesional steroids, hydroxychloroquine, topical calcineurin inhibitors, topical or oral retinoids, thalidomide and surgical excision 5,6 .Winchester et al. reported on the efficacy ustekinumab, an inhibitor of IL-12 and IL-23 7 .
This case highlights the discrepancies of CD 123 positivity and absence of transepidermal elimination of elastin in HLE.

Amendments from Version 1
We appreciate the time and effort of the referees and we believe that addressing and accepting their suggested revisions has greatly enhanced the quality of our manuscript.Following the reviewer's suggestions, the second version of this report contains a figure displaying positive CD123 immunohistochemistry in control tissue and negative CD123 immunohistochemistry in our reported case of hypertrophic lupus erythematosus.We have changed the title and corrected a previous error stating ustekinumab as a TNF-alpha inhibitor.

Current Referee Status:
Referee This report describes a case of hypertrophic lupus erythematosus based on clinical and histopathologic criteria that is negative for CD123 and elastin elimination.Negative data is important.However, as the emphasis is on the lack of CD123 and the lack of transepidermal elastin elimination, it would be good to show the negative results.For the CD123 stain, it would be good to show a positive control to make sure that the antibody really worked.

I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
No competing interests were disclosed.The order of treatment described for HLE is confusing.would start with hydroxychloroquine, then add quinacrine to hydroxychloroquine, with topicals as adjunctive therapy.Oral retinoids, thalidomide, and immuosuppressives would be options.Given that frequently there are multiple lesions that may actually koebnerize in a surgical scar, one would not include surgical excision as an option.
The report cited in favor of TNF-alpha inhibitor is on ustekinumab, which is not a TNF inhibitor.This needs revision.
Information about the antibody used for CD123 staining, as well as whether frozen or fixed tissue was used, is important.Anti-CD123 staining is not as good on fixed tissue.Were there any positive controls stained simultaneously?I have read this submission.I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
No competing interests were disclosed.

Competing Interests:
1 Comment , UAMS, USA Jerad Gardner Posted: 28 May 2014 Thank you for your commentary.The title has been changed to more clearly reflect the absence of transepidermal elimination in this case.The treatments listed in the report were a review of treatment options from the literature.They were not ordered as a suggested line of therapy.Ustekinumab has been reported to improve the plaques of hypertrophic lupus erythematosus.It is an inhibitor of IL-12 and IL-23.This fact has been corrected.We performed CD 123 staining on paraffin embedded tissue which is the method employed in her report on the novel use of Ko et al.CD 123 staining in hypertrophic lupus erythematosus.The second version of this report will contain a figure displaying positive control staining and negative CD 123 staining of the biopsy from this case.
No competing interests were disclosed.Competing Interests:

Figure 2 .
Figure 2. Histological photo of hypertrophic lupus erythematosus.Hypertrophic lupus erythematosus displays epidermal acanthosis and expansion of follicular ostia with a superficial and deep perivascular and periappendageal intradermal lymphocytic infiltrate (hematoxylin and eosin, 40× magnification).

Figure 1 .
Figure 1.Clinical photo of hypertrophic lupus erythematosus.Hypertrophic lupus erythematosus presenting as a verrucous plaque on the patient's elbow.
HLE was first described by Bechet in 1940 3 .Clinical diagnosis can be challenging as HLE can mimic psoriasis or even squamous cell carcinoma.Uitto et al. described two histological patterns of HLE One resembled hypertrophic lichen planus, while the other was similar to keratoacanthoma 4 .Daldon et al. found that transepidermal elimination of elastin was present in 14 cases of HLE 1 .Recently, Ko et al. reported that a band of CD123 positive cells at the dermalepidermal junction was characteristic of five cases of HLE 2 .

Responses for Version 2 F1000Research 2 .
Theresa Lu Autoimmunity and Inflammation Program and Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA Approved: 18 June 2014 18 June 2014 Referee Report: doi:10.5256/f1000research.4723.r5159The authors have now addressed all the concerns.I have read this submission.I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.No competing interests were disclosed.Competing Interests: Victoria Werth Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA Approved: 17 June 2014 It might also be worth commenting on this paper by Miyashita A (2013, ) et al.Acta derm venereal It might also be worth commenting on this paper by Miyashita A (2013, ) et al.Acta derm venereal in which the authors showed patients with CD123 positive cells responded better to treatment than patients with low CD123.Do you think any of this could be supported or refuted by your cases?I have read this submission.I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard.No competing interests were disclosed.Competing Interests: Referee Responses for Version 1 Theresa Lu Autoimmunity and Inflammation Program and Pediatric Rheumatology, Hospital for Special Surgery, New York, NY, USA Approved with reservations: 29 April 2014 29 April 2014 Referee Report: doi:10.5256/f1000research.3507.r4445 you for your commentary.The second version of this report will contain a histological photo of the positive control and negative CD 123 staining of the biopsy specimen.No competing interests were disclosed.Competing Interests: Victoria Werth Victoria Werth Department of Dermatology, University of Pennsylvania, Philadelphia, PA, USA Approved with reservations: 14 April 2014 14 April 2014 Referee Report: doi:10.5256/f1000research.3507.r4229This is a case of hypertrophic lupus erythematosus that is described as unusual in pathologic presentation.The title needs to indicate absence of transepidermal elimination of elastin.It is currently unclear if transepidermal elmination of elastin was present.