INTRODUCTION

Erythromelalgia is a very rare and painful syndrome characterized by symmetrical burning, swelling, and erythema of the distal extremities [1]. Erythromelalgia is classified into two forms: familial (primary) and acquired (secondary). Primary erythromelalgia is a genetic disorder caused by a mutation in the gene SCN9A that encodes a voltage-gated sodium channel [2,3]. Secondary erythromelalgia is associated with other comorbidities such as connective tissue disorders, drug reactions, infections, neoplasms, and toxin exposures [4].

Epidemiologic data on erythromelalgia is limited with an incidence estimated at 1.3 per 100,000 people in the United States [5]. Currently, there is no effective cure for erythromelalgia. Thus, treatment management is extremely challenging and mainly focused on easing the symptoms. Therefore, early diagnosis is key to relieving the patient’s symptoms. Often, in order to relieve pain, patients will treat the affected areas by immersing the extremities in cold water.

Although it may bring relief, this method poses a potential danger as it may cause skin ulcers and infection especially if done repetitively [6,7].

In this report, we discuss the treatment of HSV (herpes simplex virus) infection in a patient with recurrent secondary erythromelalgia. Parallel with the HSV infection, the patient was experiencing an inflammatory episode due to erythromelalgia. The HSV infection was treated with the administration of valacyclovir and, interestingly, as was the erythromelalgia. Among the patient’s coexisting conditions, no clinical signs or symptoms were mentioned after valacyclovir treatment. To our knowledge, this was the first case of secondary erythromelalgia-HSV association and treatment in the literature.

CASE REPORT

A fifty-year-old male patient presented with severe erythema, burning, and painful sensation on his palms bilaterally (Fig. 1a). The soles of the feet were not affected. Examination revealed penile edema with an oozing hemorrhagic vesicle of the glans penis (Fig. 1b) with obvious and painful small erosions on his lips (Fig. 1c).

Figure 1: (a) Clinical image taken upon the patient’s initial visit. The right palm is shown with visible erythema present. (b) Clinical image taken upon the patient’s initial visit. A hemorrhagic vesicle on the inferior glans penis is oozing and visible. (c) Clinical image taken upon the patient’s initial visit. Small erosions are present and visible. The erosions are more prominently seen on the superior lip.

The patient began to have a similar episode five years previously. which had been diagnosed as a herpes simplex viral infection and successfully treated with valacyclovir. According to his medical history, the patient suffered from dyslipidemia, diabetes mellitus, and depression. Additionally, the patient had a surgical history of coronary stent placement. At the time of the examination, the patient had been taking medications that included rosuvastatin, acetylsalicylic acid, lamotrigine, and lithium. No known drug allergies were documented, and the patient reported a history of smoking.

The clinical examination findings did not correlate with HSV symptoms. Biochemical and immunological tests were conducted as well as the following supplementary tests: syphilis, HIV, HBV, HCV, CMV, EBV, HSV, and Coxsackie. All lab results were normal with the exception of an increased HSV1 IgG level.

A single dose of betamethasone acetate and betamethasone sodium phosphate IM injection in combination with valacyclovir was administered. The dosing was 1 gram twice daily for 5 days. The patient was also advised to take water baths in 0.9% normal saline twice a day for the penis in conjunction with the elevation of the hands and exposure of the affected area to cool water for short periods of time. On the 10^th-day follow-up visit, all of the patient’s symptoms had subsided with considerable relief from the erythema and pain. The patient had complete healing of all lesions.

DISCUSSION

The pathophysiology of erythromelalgia is not fully understood. A study performed in 1987 investigating secondary level students in rural China reported an onset of pharyngitis prior to the symptoms of erythromelalgia. This suggested a possible connection of erythromelalgia to respiratory tract infections during the winter months. Upon testing, erythromelalgia associated poxvirus had been found in the patients’ throat swabs [7]. Likewise, case reports of secondary erythromelalgia in HIV-positive patients have been documented in the literature [8,9].

After a thorough review of the literature, this appears to be the first case report of an association between secondary erythromelalgia and HSV infection. The patient’s symptoms included erythema, pain, and edema of the palms. Along with this, the lesions on his genitals and lips gave an atypical clinical presentation of HSV infection. After the treatment with antiviral medications, all symptoms improved. There were no subsequent clinical findings of lesions, and therefore, HSV-induced erythromelalgia was suspected.

CONCLUSION

Being that erythromelalgia is an extremely difficult syndrome to treat, any intervention that shows potential aid is of interest. Current treatments only allow symptom management and not a curative solution. Other complications include primary erythromelalgia being resistant to treatment and repeated attempted cooling efforts of the skin such as ice water immersion leading to ulceration, necrosis, and gangrene [10]. The case report presented suggests that an active HSV infection may be among the conditions that may cause or trigger secondary erythromelalgia. Based on this report, erythromelalgia may coexist with genital and lip lesions that may be induced by HSV. Further studies are necessary to support the association of erythromelalgia with viral infections as well as the potential use of antivirals, such as valacyclovir, for treatment.

REFERENCES

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4. Leroux MB. Erythromelalgia:A cutaneous manifestation of neuropathy?An Bras Dermatol. 2018;93:86-94.

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6. Ito M, Yamaguchi S, Omine T, Miyagi T, Arakaki O, Yamamoto Y, et al. Behavioral therapy ceased cold water immersion dependence in a patient with familial erythromelalgia caused by SCN9A mutation. JAAD Case Rep. 2019;5:806-8.

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