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Received：March 22, 2017, Revised：June 26, 2017, Accepted：July 8, 2017

Corresponding to：Yong-Yon Won, Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 23 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea. E-mail：hackmen@naver.com

Copyright ⓒ 2018 by The Korean College of Rheumatology. All rights reserved.This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Case ReportpISSN: 2093-940X, eISSN: 2233-4718Journal of Rheumatic Diseases Vol. 25, No. 1, January, 2018https://doi.org/10.4078/jrd.2018.25.1.69

Coexistence of Erythromelalgia and Raynaud’s Phenomenon in a Systemic Lupus Erythematosus Patient

Yong-Yon Won1, Eun-Jae Shin2, Ki-Heon Jeong2, Min Kyung Shin2

1Department of Dermatology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 2Department of Dermatology, Kyung Hee University School of Medicine, Seoul, Korea

Erythromelalgia (EM) is an uncommon disorder characterized by redness, heat, and painful extremities with intense burning sensation. Attacks of EM may be worsened by limb warming, exercise, or dependency of the affected extremity. Although the coexistence of EM and Raynaud’s phenomenon (RP) may appear to be opposites in symptomatology and clinical presentation, recent studies provide an explanation based on a dysfunction of the regulation of vasomotor tone. Here, we report a case of EM in a patient with RP. (J Rheum Dis 2018;25:69-72)

Key Words. Erythromelalgia, Raynaud’s phenomenon, Systemic lupus erythematosus

INTRODUCTION

Erythromelalgia (EM), an uncommon disorder first de-scribed by Mitchell in 1878, is characterized by redness, heat, pain, and an intense burning sensation in the ex-tremities. Exacerbation of symptoms may occur follow-ing warming of a limb, exercise, or placing the affected ex-tremity in a dependent position [1]. It usually occurs in the lower extremities and less commonly affects the up-per extremities, as well as the face and ears [2]. Primary EM, usually showing symptoms in childhood, is a rare au-tosomal dominant inherited disease caused by mutations in the SCN9A gene that encodes a voltage-dependent so-dium channel α-subunit [3]. Secondary EM is related to various disorders, viz., thrombocythemia, myeloprolifer-ative disorders, arterial hypertension, vasculitis, and sys-temic lupus erythematosus (SLE) [4].Compared to EM, the most prominent symptom of

Raynaud phenomenon (RP) is whiteness of digits occur-ring as a result of cold-induced vasoconstriction, some-times followed by cyanosis and rubor of fingers. However, RP and EM are similar in some respects. Sometimes in

some patients with RP, the greatest discomfort occurs with warming the affected limb—a feature it shares with EM [5]. Although both RP and EM can occur in patients with SLE, only a few cases of both conditions coexisting in the same patient have been reported [5-8]. We present a case of a patient with SLE showing coexistence of RP and EM.

CASE REPORT

A 59-year-old woman was referred to our Dermatology Department due to a burning sensation accompanied by edema and redness on her palms and soles. Her symp-toms first occurred 15 days prior to her presentation and were usually exacerbated by warm temperatures and re-lieved by cooling. Her past medical history included is-chemic dilated cardiomyopathy and a 20-year history of RP. Her family history was negative for EM, RP, or other diseases. Although the history of her medication was not clear, there was no change of the medication in recent years. Physical examination showed symmetrical eryth-ematous patches with bean- to pinpoint-sized violaceous

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Figure 1. (A) Diffuse redness with mild swelling on the both sole. (B) Grouped bean sized violaceous macules on the medial sideof right heel. (C) Bluish cyanotic changes on the left 2nd, 4th, and 5th fingers.

Figure 2. (A) Compact hyperkeratosis, irregular rete ridge, dilated vessels in the papillary dermis and small sized vessels with fibrinthrombi in the mid-dermis (H&E, ×40). (B) High-power view showing vessel dilatation with vessel endothelial hyperplasia, fibrin thrombi, fibrinous necrosis and mild perivascular and vascular lymphocytic infiltration (H&E, ×100).

macules on both soles and palms (Figure 1A and 1B), and ulceration with atrophie blanche lesions on bilateral mal-leolar areas. She sometimes noticed cyanotic changes in her fingers consistent with a history of known RP (Figure 1C). A punch biopsy obtained from a violaceous macule on her right second finger revealed vascular dilatation with endothelial hyperplasia, fibrin thrombi, fibrinous necrosis, and positive immunoglobulin G (IgG), and IgM in the vessel walls noted on immunofluorescence stain-ing—findings consistent with livedoid vasculitis (Figure 2). Another skin biopsy performed on an erythematous swollen patch on her sole revealed histological findings of

only dermal ectatic vessels (Figure 3). Laboratory inves-tigations revealed: hemoglobin (8.7 g/dL), platelet count (78×103/μL), C3 (28.1 mg/dL), and C4 (15.3 mg/dL) were decreased while antinuclear antibodies (1:320), per-inuclear anti-neutrophil cytoplasmic antibodies, anti-dou-ble-stranded DNA antibodies, and direct Coombs test were positive. Peripheral blood smear (PBS) revealed nor-mochromic normocytic red blood cell. C-reactive protein (5.93 mg/dL) and 24 hour urine protein (2,048 mg/day) were also elevated. These findings met two clinical cri-teria (renal, thrombocytopenia) and four immunological criteria (anti-nuclear antibodies, anti-DNA, low comple-

Coexistence of Erythromelalgia and Raynaud’s Phenomenon

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Figure 3. Scattered dilated vessels in the upper dermis (H&E, ×100).

ment, direct Coombs test) based on the 2012 systemic lu-pus international collaborating clinics diagnostic criteria for SLE. Finally, we made a diagnosis of secondary EM and secondary RP with SLE accompanying livedoid vasculitis, which is one of the non-specific skin symptoms indicating systemic activity of SLE. In rheumatology, for the treatment of SLE, she was pre-

scribed 400 mg hydroxychloroquine per day and 50 mg prednisolone per day, which led to an improvement of livedoid vasculitis and erythromelalgia.

DISCUSSION

Lupus erythematosus is classified as acute, subacute, or chronic cutaneous lupus erythematosus based on distinc-tive histological findings, and as a non-specific skin dis-ease when no characteristic histological findings are ob-served [9]. Non-specific skin symptoms associated with lupus erythematosus are mainly observed in SLE and are important symptoms from a dermatologist’s viewpoint because they are critical indicators of disease activity. Cutaneous manifestations related to, but not specific to SLE, include cutaneous vasculitis, periungual telangi-ectasia, urticarial vasculitis, livedo reticularis, atrophie blanche, and bullous lesions [10]. RP is also seen in 15% to 30% of patients [11] and EM is rarely observed [12].Based on criteria proposed by Kurzrock and Cohen [1],

EM is clinically diagnosed in patients showing: (i) Severe burning discomfort, warmth, and erythema of the feet and/or hands. (ii) Exacerbation and aggravation of symp-toms upon exposure to heat or placing the involved ex-tremity in a dependent position. (iii) Amelioration of dis-

comfort by elevation or cooling of the affected extremity.EM may be primary or secondary in nature. Primary EM

usually affects younger patients and is more often bilateral. Secondary EM is related to various disorders, such as thrombocythemia, myeloproliferative disorders, arterial hypertension, vasculitis, and SLE [4], and admin-istration of calcium channel blockers or bromocriptine [13,14]. A negative family history, late onset at the age of 59 years, and clinical symptoms of SLE indicated the pres-ence of secondary EM in the patient we reported in our study. In this case, hematologic disease could be ruled out as a cause of EM because normochromic normocytic red blood cell was revealed in PBS and any disease increasing blood viscosity, such as thrombocythemia or polycythe-mia vera, was not observed. She had a long history of di-lated myocardiopathy, so calcium channel blocker or beta blocker medication should also be taken into consideration. However, since there was no history of medication change in recent years, the medication could be ruled out as a possible cause of EM.Similar to EM, RP maybe (i) primary (formerly known as

Raynaud’s disease), or (ii) secondary (formerly known as Raynaud’s syndrome). Primary RP most typically affects female patients in the first and second decades, often with a family history of the disease and is always symmetric. Secondary RP is most commonly associated with con-nective tissue disorders and less frequently with throm-boangiitis obliterans, thoracic outlet syndrome, paraneo-plastic syndrome, hypothyroidism, administration of be-ta blockers or ergotamines, and exposure to vibrating ma-chinery [5]. Our patient related no family history and showed an asymmetric pattern of RP; thus, she was more likely to have secondary rather than primary RP.Although RP and EM are both vascular acrosyndromes,

EM is a rare painful disorder of the extremities charac-terized by redness, a burning sensation, and increase in skin temperature exacerbated by exposure to heat [15]. Unlike EM, in patients having RP, the characteristic symp-toms of pallor or cyanosis are aggravated by cold. Therefore, some authors believe that the coexistence of RP and EM is simply coincidental [8]. However, recent studies provide an explanation for the rare instances in which EM and RP are seen to coexist. Berlin and Pehr [5] have postulated that both syndromes have a common ba-sis in that in both conditions, there is a dysfunctional reg-ulation of the vasomotor tone. In both, EM and RP, the in-itial event seems to be vasospasm. Subsequent to vaso-constriction, reactive hyperemia may occur in both con-

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ditions, although it is more apparent and longer lasting in EM. In this case, the patient had livedoid vasculitis with histologic findings of fibrin thrombi and vasculitis. It is thought that this vascular obstructive condition caused vasospasm associated with the development of RP and EM.

SUMMARY

In summary, we report a case of EM in a patient with RP, which is supposed to be in the same spectrum of diseases involving a dysfunctional vasomotor tone like EM. Pathophysiological mechanisms underlying both, RP and EM are not yet clearly understood, and further studies may be helpful in understanding the pathophysiology of the two diseases.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

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