Rowell syndrome - case report and review of the literature
1. Department of Dermatology and Venereology, Hospital São João, Oporto, Portugal. email@example.com
2. Department of Dermatology and Venereology, Hospital São João and Faculty of Medicine, Oporto University, Portugal
Rowell syndrome is a rare distinctive entity first described in 1963 by Rowell and coworkers. It consists in erythema multiforme-like lesions associated with lupus erythematosus. Zeitouni et al. recently redefined the major and minor diagnostic criteria. Major criteria are lupus erythematosus, erythema multiforme-like lesions and speckled pattern of antinuclear antibody. Minor criteria are chilblains, positive anti-La (SS-B) or anti-Ro (SS-A) antibody and reactive rheumatoid factor. We report a case of a 63-year-old woman, with no previous history of lupus erythematosus, who developed erythema multiforme-like lesions and laboratory findings consistent with Rowell syndrome.
In 1963 Rowell and coworkers reported a new syndrome characterized by erythema multiforme-like lesions, discoid lupus, positive test for rheumatoid factor (RF), speckled antinuclear antibodies and a positive saline extract of human tissue (anti-Sj-T) . Subsequently Rowell syndrome (RS) was described in patients with systemic lupus erythematosus and subacute lupus erythematosus .
Cases of lupus erythematosus (LE) and erythema multiforme (EM) have been reported since 1922 and some believe that criteria of RS simply reflect a coincidence [1, 2, 3, 4]. However, the reported clinical and immunological findings in some patients have led many authors to conclude that Rowell syndrome is indeed a rare and distinctive entity .
Recently Zeitouni and coworkers redefined major and minor diagnostic criteria. Major criteria are defined by the coexistence of lupus erythematosus, erythema multiforme-like lesions and speckled pattern of antinuclear antibodies. Minor criteria includes chilblains, positive anti-La (SS-B) or anti-Ro (SS-A) antibodies and reactive RF. The diagnosis of this syndrome requires the presence of all the major criteria and at least one of the minor .
We report a 63-year-old Caucasian woman admitted to our department with a 6-week history of widespread, pruritic, erythematous skin rash, without systemic symptoms. She was taking alprazolam and paroxetin for many years to treat her depressive condition. She had no history of lupus, photosensitivity disorder or other significant disease. There was no apparent precipitating event. Family history was not contributory.
Physical examination revealed erythematous, well-defined and confluent papules, some resembling target lesions, with blister formation and central necrosis, symmetrically distributed on the face, trunk and limbs (Fig. 1A and 1B). Palms and soles were spared. There were no chilblains or mucosal lesions.
Skin biopsies obtained from the leg and chest showed keratinocyte necrosis, edema of the dermis and a focal perivascular lymphocytic infiltrate near the basal layer (Fig. 2A and 2B). Direct immunofluorescence study was negative.
Laboratory investigations revealed mild leucopenia (white cell count 3.25x109/ml) and thrombocytopenia (platelets 140x109/ml). Erythrocyte sedimention rate was increased (50 mm/h). Serum protein levels, renal and hepatic function and urinalysis, tumoral markers and coagulation study were within normal ranges. Viral serologies, including hepatitis B and C and human immunodeficiency virus, cytomegalovirus, herpes simplex virus (HSV) and Epstein Barr virus were negative. Detection of antibodies to Mycoplasma pneumonia was also negative.
Autoimmune screening demonstrated the presence of antinuclear antibody (ANA) in a speckled pattern (1:320 dilution), elevated anti-DNAds antibody (1435.3 UI/ml) and positive anti-Ro antibody (anti-SSA). Rheumatoid factor, anti-La (anti-SSB), anti-SM, anti-RNP and anti-SL70 antibodies were all negative. Complement levels were normal.
Chest X-ray, abdominal ultrasound and electrocardiogram did not reveal any abnormality. Echocardiogram showed slight mitral insufficiency.
A course of oral prednisolone (80 mg per day) and topical bethametasone ointment was started, with a slow resolution of the cutaneous lesions. After one month of oral prednisolone the eruption cleared leaving a mild residual post-inflammatory hyperpigmentation, but no scars. Tapering doses of oral prednisolone were giving for more two weeks after total resolution. Since then no recurrences have been noticed during a follow-up period of more than one year.
The RS diagnosis is in this case supported on clinical and immunologic features. The speckled pattern of ANA is the most consistent laboratory feature of this syndrome [2, 5], and it was present in our patient additionally to a positive anti-Ro.
Clinical lesions of RS include LE (systemic, discoid or subacute), EM-like lesions and chilblains. Although this syndrome was originally described in a discoid erythematous lupus (DEL) patient by Rowell , further cases with different variants of cutaneous LE such as systemic (SLE) and subacte (SCLE) were reported . At admission a diagnosis of SCLE was considered in our patient due to the presence of elevated anti-DNAds antibody, speckled pattern of ANA, positive anti-Ro and a skin rash. Leucopenia, thrombocytopenia, as well the history of a depressive syndrome is consistent with the diagnosis. Bullous erythematous lupus was excluded by the findings on skin biopsy and direct immunofluorescence.
Classical EM is precipitated by trigger factors such as infectious agents (mainly Mycoplasma pneumonia and HSV) or drugs (mainly antibiotics, non steroid anti-inflammatories and anti-convulsivants), although other causes including malignant conditions and connective tissue disease have been implicated [2, 3, 6, 8, 9, 10, 11]. EM is not associated with any specific auto-immune serological abnormality . The prolonged course (more than six weeks) of erythema multiforme-like lesions observed in our patient does not favor the diagnosis of true erythema multiforme [1, 3, 12]. On the other hand there was no identifiable precipitating factor.
Clinical and histological differentiation of EM from SCLE may be difficult [3, 5, 13]. Early SCLE lesions with annular-polycyclic pattern may resemble EM. Necrotic keratinocytes may be found in SCLE lesions  as in EM. In fact, Herrero and coworkers recently described the presence of necrotic keratinocytes in 6 of 13 (54%) SCLE patients . As some clinical, histological and immunological findings seems to overlap RS and SCLE, it has been suggested by some that lupus eythematosus with EM-like rashes designated as RS represent a subset of SCLE with targetoid lesions, rather than a distinct entity [3, 12, 15].
Although most case reports do not mention the presence or abcense of chilblains, Zeitouni and coworkers agree that chilblains should be included as a minor diagnostic criteria . It has been hypothesized that the speckled ANA factor may be part of the immunologic disturbance contributing to the formation of chilblain lesions . Additionally, most patients with chilblains often have a positive RF. Therefore, it is possible that both the speckled ANA pattern and RF are actually associated with perniosis [3, 6]. In fact chilblains are one of the more commonest cutaneous manifestations in the spectrum of LE, and speckled ANA and RF are strongly associated with the chilblain lupus variant and should not be considered as a specific criteria .
Zeitouni and coworkers reviewed diagnostic criteria for RS . They proposed three major and three minor criteria. The major criteria consist in the presence of LE (systemic, discoid or subacute), EM-like lesions (with or without involvement of mucous membranes) and speckled pattern of antinuclear antibody. The minor criteria includes chilblains, anti-Ro and/or anti-La antibodies and positive RF. All three major criteria and at least one minor criteria are required to establish the diagnosis of RS [2, 3, 4, 7]. Our patient had all the three major and one minor criteria (anti-Ro antibody), thus fulfilling the requirements for diagnosis. To the best of our knowledge, approximately 33 cases of LE occurring in association with EM have been diagnosed as RS , although not always respecting the criteria proposed by the different authors [5, 6, 7, 13].
In the literature RS patients are predominantly middle-aged women [1, 2, 5, 7, 13], however it as also been described in younger women [4, 7] corresponding to the period of LE onset in general population , and even in pregnant women [1, 4]. RS has been described rarely in men. Although oral, eye and vulval lesions are infrequent features of RS, mucosal involvement has been demonstrated in 47 percent of the cases .
Patients with lupus erythematosus may develop coincidental erythema multiforme . However, if characteristic serological abnormalities are present and there is no obvious precipitating factor, RS should be considered [2, 4]. Most patients did well and respond to therapy with corticosteroids and antimalarials [2, 3, 5, 6, 10, 11, 12, 13, 15], with only a few complications related to LE or EM . Zeitouni and coworkers described a case of RS responding to dapsone . In our patient the lesions completely resolved with oral prednisolone plus topical bethametasone.
Recently, Mandelcorn and coworkers have described a more severe variant of Rowell syndrome characterized by an acute progression to toxic epidermal necrolysis in two patients .
Previous reports showed that in patients with this syndrome, DLE usually has a recurrent and chronic course, and SLE is more active and difficult to control [3, 4, 6]. Our patient had SCLE that in the setting of RS has a favorable prognosis, although it can relapse at various intervals over its course for up to twenty years, without any seasonal influence [1, 2, 3]. Our patient has been without lesions for more than one year.
A drug reaction to alprazolam and paroxetin was initially considered. However the disease did not improve on discontinuation of these medications and did not aggravate with their reintroduction.
Rowell syndrome is rare. As more cases are reported, the existence of this entity will be further clarified [2, 4]. For now it should be considered a distinct disorder, suspected and screened in all patients with LE and EM-like lesions, with no evidence of a precipitating factor.
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