Erythromelalgia

Abstract

A Hispanic man with a twenty-eight year history of systemic lupus erythematosus (SLE) and a high titer of anticardiolipin IgG antibodies was noted to have reticulate and stellate acral pigmentation. The patient reported that hand swelling and erythema developed soon after the diagnosis of SLE was established. This episode resolved quickly without recurrence or immediate sequelae. We postulate that this eruption was related to SLE and anticardiolipin antibodies. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anticardiolipin antibodies, or a consequence of therapy.

Case report

A 54-year old Hispanic man with a twenty-eight year history of systemic lupus erythematosus (SLE) presented with smudgy blue-black pigmentation of his ten proximal nail folds and fingertips. A diagnosis of SLE had been made previously based on: 1) proteinuria; 2) positive RPR with no evidence of syphilis and anticardiolipin antibodies; 3) arthritis; and 4) a positive ANA. Besides proteinuria and positive RPR and anticardiolipin antibodies, no other symptoms of SLE had been present for a decade. He noted that soon after the diagnosis of SLE was established, he experienced hand swelling and erythema. These symptoms resolved quickly without treatment, recurrence, or apparent sequelae. He could not recall exactly when the hyperpigmentation of his proximal nail folds developed. He denied any other acral rashes, including livedo reticularis, leg ulcers, necrotizing purpura, distal cutaneous ischemia, peripheral gangrene, thrombophlebitis, or hemorrhage, or family history thereof (1).

His prior therapy for SLE consisted of azathioprine, clonidine, and cimetidine for many years. Prednisone was used initially to treat acute manifestations of SLE, but not during the previous decade. During the one year prior to visiting us, the patient received an 8-week course of minocycline for folliculitis, as well as a 4-week trial of oral terbinafine and topical oxiconazole for less than 4 weeks for toe onychomycosis.

On physical examination, the patient appeared well; however, his proximal nail folds possessed a fine, wiry blue-black macular network corresponding in location to the underlying capillary vessels (Fig 1). Similar macular hyperpigmentation on the fingertips assumed a reticulate and stellate pattern (Fig 2). The patient's toenails showed distal onycholysis without the pigmentation observed on his fingers. The integument examination was otherwise unremarkable.

[FIGURE 1-2 OMITTED]

Notably, anticardiolipin IgG antibody was 95 GPL (normal range: 0-14), although no current clinical manifestations of the antiphospholipid syndrome were present. Complement levels, anticardiolipin IgM antibodies, dsDNA, antinuclear antibody, rheumatoid factor, lupus anticoagulant, anti-SS-A, and anti-SS-B were negative or normal. An undiluted RPR was reactive and FTA-ABS was minimally reactive, findings recognized in SLE that do not indicate a history of lues (2). The patient denied any history of syphilis, had not been treated for syphilis, claimed having had only one sexual partner (his wife), and his wife had no evidence of syphilis. Routine urinalysis revealed 3+ protein and 1+ hemoglobin. The cause of microscopic hematuria was not ascertained after exhaustive urologic studies.

A 3 mm biopsy of the proximal nail fold showed variable degrees of epidermal melanin (Fig 3). A Fontana stain highlighted small amounts of dermal granular melanin. The microscopic diagnosis was consistent with post-inflammatory pigment alteration but did not reveal more specific changes of connective tissue disease. No hemosiderin or mucin was present.

Discussion

Acral hyperpigmentation is occasionally seen in association with Wilms' tumor and vitamin B12 deficiency (3). Certain inherited pigmentary anomalies, such as the reticulate acropigmentation of Kitamura, manifest as a network of brown macules randomly distributed on the hands (4). A number of drugs have been associated with confluent acral pigmentation, including phenytoin, Adriamycin, and tegafur (5). Minocycline, a medication briefly taken by the patient, commonly causes blue-gray pigmentation of the nail bed and plate; however, a recent review regarding minocycline and pigmentation did not associate it with hyperpigmentation of the nail folds (6). The rare induction of lupus erythematosus by minocycline also has not been associated with nail changes (7). Microscopically, these acral conditions show diffuse increases in melanin and melanophages in the dermis and/or epidermis thought to be secondary to antecedent epidermal inflammation. The most distinctive finding in our case is the unique stellate, reticulate, and wiry patterns of pigmentation confined to the nail folds and finger tips.

Acral collections of melanin and melanophages have not been described as cutaneous manifestations of anticardiolipin or antiphospholipid antibodies. Antiphospholipid antibodies interfere with coagulation, leading to a wide range of disorders which may include livedo reticularis, livedo vasculitis, atrophie blanche, thrombophlebitis, skin ulcers, gangrene, hemorrhage, and cutaneous necrosis (1). Microscopically, these changes appear as fibrin deposition and intravascular thrombosis, typically without vasculitis (8). There can also be a reactive vascular proliferation around thrombosed vessels (8).

Patients with SLE in the absence of anticardiolipin and antiphospholipid antibodies manifest a variety of acral findings. These findings include: subcutaneous nodules, Raynaud's phenomenon, nail fold capillary hemorrhages, focal necrosis, prominent capillary loops, chilblains (perniosis), white nails, ragged or hyperkeratotic cuticles, splinter hemorrhages, nail pitting, nail ridging onycholysis, striate leukonychia, recurrent Osler's nodes, clubbing, gangrene of the finger or toe tips, erythromelalgia, calcinosis, and reticulate telangiectatic erythema (10). Other recently described findings include red lunulae (11), papular mucinosis (12), and pterygium inversum (13).

In 1990, Vaughn described diffuse blue-black chromonychia in a cohort of African-American patients with SEE (14). A subset of these patients had telangiectasias and atrophy of the proximal nail fold, in some instances with acral hypopigmentation and hyperpigmentation, several of whom described prior ulceration(s). Like our patient, most of the subjects with chromonychia and nail fold changes were unsure of the duration. Vaughn did not actively investigate the etiology of the rash or check anticardiolipin or antiphospholipid antibodies.

The pathogenesis of reticulate hyperpigmentation in our case remains elusive. The uncertain onset complicates the assessment of medication effects. While the pattern of pigmentation of this acral rash is reminiscent of perniosis found in SLE, it lacks the characteristic lymphocytic vasculitis. A vasculopathic origin of this rash is suggested by the pattern of pigmentation that seems to track the capillaries around the nail beds and the history of hand swelling and erythema. A condition that combines vasculitis and acral macules with elevated titers of antiphospholipid antibodies has been termed unfading acral microlivedo (15). The histopathology of this skin finding is marked by microthrombosis in dermal vessels without inflammation. Since the pigment changes in our case have been stable for many years, it is not surprising that microthrombosis is absent. We speculate that reticulate and stellate acral pigmentation could be the sequela of acral microlivedo and propose that this pigmentation should be considered among the dermatoses associated with SEE.

References

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(15.) Grob JJ. San Marco M, Aillaud MF, Andrac L, Gabriel B, Juhan-Vague I, et al. Unfading acral microlivedo. A discrete marker of thrombotic skin disease associated with antiphospholipid antibody syndrome. J Am Acad Dermatol 1991; 24:53-8.

NOAH S SCHEINFIELD JD MD (1), DAMIAN D DICOSTANZO MD (2), AND STEVEN R COHEN MD MPH (3)

(1) ASSISTANT CLINICAL PROFESSOR OF DERMATOLOGY, COLUMBIA UNIVERSITY SAINT LUKES ROOSEVELT HOSPITAL, NEW YORK, NEW YORK

(2) ASSISTANT CLINICAL PROFESSOR OF DERMATOLOGY ALBERT EINSTEIN COLLEGE OF MEDICINE, JACOBI MEDICAL CENTER, BRONX NEW YORK

(3) PROFESSOR OF DERMATOLOGY, MOUNT SINAI SCHOOL OF MEDICINE, NEW YORK, NEW YORK

ADDRESS FOR CORRESPONDENCE:

Noah Scheinfeld

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