Case Discussion
SLE is a chronic, recurrent, potentially fatal multisystem autoimmune and inflammatory connective tissue disorder whose diagnosis can be difficult due to the broad range of clinical manifestations and the lack of pathognomic features or specific laboratory tests (6–8). Before puberty, the female-to-male ratio of SLE occurance is 3:1; after puberty, the ratio increases to 9:1. SLE is generally classified into chronic cutaneous LE (CCLE), subacute cutaneous LE (SCLE), and acute cutaneous LE (ACLE) (6,7).
The kidneys, brain, lungs, heart, skin, and joints are the major organs affected by SLE, with commonly presenting symptoms including fatigue, fever, arthralgias, myalgias, weight loss, rash, oral ulcers, thrombocytopenia, and leucopenia. The mainstay of laboratory testing for the diagnosis of SLE is the assessment of ANA. While a positive ANA test result is useful in diagnosis, it is not specific for SLE. In contrast, anti-ds DNA is relatively specific for SLE (8). Up to 30% of patients will present with cutaneous symptoms, including butterfly-shaped facial rash, red macules, papules, and plaques, alopecia, and mucosal ulcers. (5)
In the case of the patient, the likely diagnosis of SLE was made based on the clinical presentations, including fever, oral ulcers, and a positive anti-ds DNA.
EM, on the other hand, is an acute, immune‑mediated mucocutaneous condition characterized by the presence of multiple symmetric, typical, or atypical target lesions with or without crusting at the center of the lesion and concentric color variation mainly on extremities (hands, feet, and the extensor aspects of limbs), with or without itching and prodromal symptoms (7).
Classical or true EM is precipitated by trigger factors such as infective agents like herpes simplex virus, mycoplasma pneumoniae, drugs like anticonvulsants, antibiotics, and non-steroid anti-inflammatory drugs, any underlying malignancy, or connective tissue disorders, and is not associated with any specific serological abnormalities commonly seen in autoimmune disease or with chilblain (6,7,9). In the case of the patient, there was no identifiable precipitating cause of erythema multiforme.
True EM is never associated with any specific autoimmune or serological abnormalities. In our patient, the skin manifestations and histopathologic findings are suggestive of EM, but the absence of any triggering factors does not favor the diagnosis of true EM.
Cases of EM associated with LE lesions where an EM trigger factor is missing, are considered a diagnostic criterion for RS (10). Rowell syndrome was originally described in 1963 by Rowell et al., who identified four females with discoid LE, EM-like lesions, and the presence of one of the following serology: speckled ANA, anti-Ro/La antibody, or rheumatoid factor (RF) (1). RS is characterized by the combination of EM, LE, and typical serological abnormalities (11).
RS is an uncommon presentation of lupus erythematosus with erythema multiforme-like lesions associated with specific serological changes, including positive rheumatoid factor (RF), speckled ANA, positive rheumatoid factor, or anti-La antibodies in the serum (7,11,12). The speckled pattern of ANA is the most consistent diagnostic feature of Rowell’s syndrome. Anti-La antibodies and rheumatoid factor seem to be less consistent features (9). In our case, the patient had a positive RF and a positive ANA with a speckled pattern.
There is a question as to whether the EM-like lesions of RS represent a subset of SCLE since vesicobullous lesions that resemble EM may occur rarely in SCLE. However, the vesicobullous lesions of SCLE do not result in clinical necrosis or scarring, and the histopathological features do not include necrosis of keratinocytes (11). Skin biopsy of the patient reveals areas of ulceration, follicular plugging, mixed inflammatory cells exocytosis, edematous, and hemorrhagic dermis with thrombi formation suggestive of inflammatory dermatoses as depicted in figure 4.
In patients with SCLE, a positive ANA is seen in 75%; the pattern is usually homogenous. Positive anti-Ro is found in 60% and a positive rheumatoid factor in 30–40%. Immunofluorescence of lesional skin reveals linear IgA, IgM, and C3 at the dermo-epidermal junction in 60% of patients. The immunofluorescence from an EM-like lesion in our patient was negative (11).
Before considering a diagnosis of RS, it is important to rule out common triggering agents and other differentials of EM. In this case, no precipitating factor for EM was identified. Also, a diagnosis of RS is based on the presence of major and minor criteria, as seen in Table 1 (1). All three major and at least one minor criteria are required to confirm RS (9).
In our patient, as all the major criteria, along with one minor criterion i.e., positive RF, were present, we consider our case to be a classic RS.
Table 1: Criteria for RS Diagnosis by Zeitouni et al. (1).