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Home , Granuloma annulare, Melasma

Mimickers

Arup Kumar Kundu, Somak Kumar Das

INTRODUCTION

Systemic is considered as “the great mimic of other conditions”. Conversely there are many diseases which can mimic SLE as a systemic disease or as dermatological, rheumatological, vasculitic, or immunological mimickers. This monograph is restricted to the lupus mimickers only, not the discussion on SLE.

DERMATOLOGICAL MIMICKERS OF S.L.E. 1,2 I. Dermatological conditions mimicking acute cutaneous lupus erythematosus (LE) : Rosacea is characterized by of the central face that has persisted for months or more. The convex areas of the nose, cheeks, chin, and forehead are the characteristic distribution [Fig. 1]. Triggers of rosacea may include hot or cold temperature, sunlight (hence, photosensitive), wind, hot drinks, spicy foods, exercise, emotions, alcohol, cosmetics, topical irritants, menopausal flushing, medications etc. Erythematotelangiectatic subtype and papulopustular subtype may mimic acute cutaneous LE. The malar erythema of lupus erythematosus [Fig. 2] can be difficult to differentiate from rosacea3. The presence of pustules and or blepharitis favors a diagnosis Fig.1: Rosacea of rosacea, while fine scaling, pigment change, follicular plugging and scarring favor a diagnosis of lupus. In occasional photodistribution. patients, histologic examination of involved skin may be Chloasma / : It is combined epidermal and dermal necessary for distinction. of forehead, cheeks, and perioral area. It Seborrheic dermatitis: Seborrheic dermatitis of the face is a common problem, almost exclusively limited to women; may closely mimic both early rosacea and the butterfly extremely prevalent in Latin America, among patients with lesions of systemic lupus erythematosus2. In contrast to mixed Indian/Spanish background. Risk factors include sun seborrheic dermatitis, lupus erythematosus rarely affects exposure, or use of oral contraceptives. This the nasolabial folds and often has a clearly demonstrable photosensitivity reactions and distribution over the face 294 Medicine Update-2011

other signs of LE appear. Direct immune-fluoroscence (DIF) studies are helpful. Some lichenoid drug eruptions have a photodistribution. The most commonly incriminated drugs include angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics, antimalarials, quinidine and gold. Tinea faciei6: This facial infection is characterized by erythematous, often with scaly patches; not annular because of facial configuration; pruritic; may worsen with light exposure. It mimics DLE which is slower to develop and more persistent; has prominent follicles, may be painful. Lupus pernio / cuteneous sarcoid: It is red-violet chronic infiltrate on tip of nose; often associated with chronic pulmonary involvement and digital bone cysts. Upon diascopy, in which pressure induces blanching, the lesions Fig.2: Facial of Systemic Lupus Erythematosus are said to have the color of ‘apple jelly’. may mimic acute cutaneous LE. II. Dermatological conditions mimicking sub-acute RHEUMATOLOGICAL AND MUSCULOSKELETAL MIMICKERS cutaneous LE OF S.L.E.7 The lesions of sub-acute cutaneous lupus erythematosus , systemic sclerosis and , (SCLE), when predominantly papulosquamous in appearance, Sjogren’s syndrome, mixed connective tissue disorder, may be similar to the appearance of photosensitive eczema dermatomyositis, polymyositis mimic features of SLE. or . Dermatophytosis, annulare, These connective tissue diseases are a family of closely erythema annulare centrifugum or other annular related disorders. These diseases have a number of common may simulate SCLE, when the lesions are predominantly features. The most common symptoms at presentation annular. include Raynaud’s phenomenon, arthralgia, or arthritis; mucocutaneous symptoms such as photosensitivity, malar III. Dermatological conditions mimicking chronic rash, alopecia, and oral ulcerations; fever sicca symptoms, cutaneous LE or discoid LE or CNS symptoms. Polymorphous light eruption, , leukemia cutis, lymphoma cutis, , , Söjgren’s Syndrome7 psoriasis, lupus vulgaris and sarcoidosis mimic chronic form Söjgren’s syndrome is a chronic autoimmune disorder of cutaneous lupus, discoid lupus erythematosus (DLE). that can occur alone (primary Sjogren’s syndrome) or Histologic and DIF evaluation are often necessary to make in association with other autoimmune diseases, most a definitive diagnosis of DLE. commonly systemic lupus erythematosus and rheumatoid Polymorphous light eruption4: Polymorphous light eruption arthritis (RA) [secondary Sjögren’s syndrome]. (PMLE) is a common, sunlight-induced eruption affecting individuals of all races. The diagnosis of PMLE is suggested Many of the clinical and serological features of Sjögren’s by its characteristic history, clinical findings, and lack of syndrome and SLE make the precise diagnosis difficult circulating antinuclear and other lupus erythematosus- because there are similarities between the two diseases. associated antibodies. Lesions of LE tend to last for weeks  Those with primary Sjögren's syndrome and those with to months, whereas PMLE lesions, in the absence of further SLE have other similar disease symptoms, including: sun exposure, usually resolve within days. Polymorphous  Arthritis light eruption may clinically simulate tumid lupus, but  Skin rash histologically the two can usually be distinguished.  Kidney disease. Lichen planus (LP)5: The disease most difficult to  Autoantibodies are common in Sjögren's, with 80% testing differentiate from LP is LE, particularly in patients with oral positive for antinuclear antibodies (ANA), Rheumatoid or scalp lesions alone. In these patients, the diagnosis of LE factor in 75% to 95%.9 may only be made after additional biopsies are performed or Medicine Update-2011 295

Lupus and Rheumatoid Arthritis7 dermatomyositis, and scleroderma, and is known as MCTD. In lupus, joint pain (arthralgia) is common. Joint swelling These persons often (but not always) have one specific (arthritis) may be present in some cases, but the majority antibody in their blood (anti-U1RNP antibody) but of those with lupus experience joint pain without swelling not the other antibodies commonly associated with SLE, or only intermittent swelling. Early rheumatoid arthritis may SSc, or PM-DM. mimic lupus. In rheumatoid arthritis, joint swelling is always present and pain is common but less prominent. Because VASCULITIC AND IMMUNOLOGIC MIMICKERS rheumatoid arthritis is more likely than lupus to cause joint This group includes primary and secondary deformities and bone destruction, joint replacement or mimicking SLE. Secondary vasculitic disorders are composed reconstructive surgery is more often required in RA than of infectious diseases and malignant diseases. Diseases in SLE. causing primary vasculitis are those described above under heading of rheumatological diseases mimicking SLE. Myositis7 Secondary vasculitides mimicking SLE are as follows: Many persons with lupus have muscle pain (myalgia), but a few have muscle weakness due to inflammation (myositis). In Infectious Diseases polymyositis-dermatomyositis (PM-DM), the primary problem  Viral: Hepatitis C, hepatitis B, parvovirus B19, HIV, infec- is proximal muscle weakness due to muscle inflammation. tious mononucleosis (Epstein-Barr Virus) Typically, there is little or no pain associated with the  Bacterial: Lyme’s disease, disseminated gonococcal weakness. People with myositis have increased blood level arthritis, atypical mycobacteria, (secondary)8 of creatine kinase with abnormal electromyogram (EMG),  Parasitic: visceral leishmaniasis associated with muscle cell degeneration with inflammation found in muscle biopsy. Characteristic pathognomonic skin Malignancy: Hematological malignancies (Hodgkin’s rash (es) is dusky red, and may appear in malar distribution lymphoma), thymoma; carcinoma of the lung, breast, mimicking the classic SLE “butterfly rash”. Shawl sign, and ovary as paraneoplastic syndromes9 may mimic SLE. A heliotrope rash, and Gottron’s sign seen over the malignancy can cause anemia, elevated ESR, positive ANA, dorsum of the PIP and MCP joints are highly suggestive of vasculitis, and other autoimmune phenomena mimicking dermatomyositis. Presences of ANA, anti-Jo1 antibody are SLE. An unusual case of disseminated gastric signet ring seen in patients with associated interstitial lung disease. cell carcinoma was reported mimicking systemic lupus erythematosus. Lupus and Scleroderma7 The hallmark of scleroderma (SSc) is thickened skin Hepatitis C mimicking lupus10: Chronic HCV infection which affects the fingers, and often the hands, forearms, does not target only the liver, but has a profound effect feet, and face due to the excessive production and on the immune system and sometimes mimics SLE. uncontrolled laydown of collagen. Classical “salt-and- Deposition of immune complexes containing cryoglobulins pepper” pigmentation is seen in SSc. The varieties of skin in different organs is the presumed disease mechanism seen in lupus are due to inflammation, rather than in mixed cryoglobulinemia, characterized by purpura, fibrosis. Other features which are less common in SLE than in arthralgias (or more rarely, arthritis), glomerulonephritis, SSc include: pulmonary fibrosis, difficulty in swallowing solid, and polyneuropathy. Unselected patients with chronic HCV and heartburn or indigestion from stomach acid “refluxing”, infection display a number of autoantibodies including and deformities of hands. Raynaud’s phenomenon occurs in antinuclear antibodies (10%). 95 percent of people with scleroderma and in 40 percent of persons with lupus. Anti-nuclear antibody is found to be Parvovirus B1911: Parvovirus B19, a virus which commonly present in both the situations; but anti-topoisomerase-1 runs an asymptomatic or benign self-limiting course such antibody (in diffuse SSc) and anti-centromere antibody (in as erythema infectiosum, transient aplastic crisis, flu-like localized SSc) are found to be present in scleroderma. symptoms, rash, arthralgia, and arthritis can present with multi-systemic symptoms resembling SLE, both clinically and Mixed Connective Tissue Disease (MCTD)7 serologically. Similarities have been so striking that patients Some individuals have symptoms and signs of more than have been initially misdiagnosed with SLE, having fulfilled one connective tissue diseases, e.g., lupus, polymyositis- 3-5 of the criteria of the American College of Rheumatology, 296 Medicine Update-2011 currently used for the diagnosis of SLE, only to discover later develop a positive ANA and at least one clinical feature that they were infected by parvovirus B19. of SLE after an appropriate duration of drug exposure, HIV12: A Sjogren’s-like syndrome, termed diffuse infiltrative and whose symptoms resolve after discontinuation of the lymphocytosis syndrome (DILS) is now a well-established drug. Antihistone antibodies are present in more than 95% manifestation of HIV infection that may present to the of cases, whereas hypocomplementemia and anti-DNA rheumatologist. The diagnosis may be missed because most antibodies are rare. A variety of drugs have been identified of these patients do not have AIDS, and may well have a as being definite, probable, or possible causes of lupus - lymphocytosis rather than a lymphopaenia. Furthermore ANA procainamide, quinidine, hydralazine, methyldopa, tumor in low titer and antiphospholipid antibodies may mimic SLE. necrosis factor-? blockers, carbamazepine, phenytoin, isoniazid, , nitrofurantoin and so many. Acute Lyme arthritis13: has been called “the new great mimicker” because its protean manifestations NEUROLOGICAL MIMICKER OF S.L.E.7,17 resemble those of other diseases. Acute Lyme arthritis Multiple sclerosis (MS) can mimic SLE. Between 5 and 10 can mimic other causes of monoarticular or pauciarticular percent of MS patients have antinuclear or anti-double- arthritis, including reactive arthritis and other seronegative stranded DNA antibodies without signs of lupus. On MRI, the spondyloarthropathies, juvenile rheumatoid arthritis, and lesions of lupus and of MS appear similar, and both the optic systemic lupus erythematosus. nerve (rarely) and the spinal cord may be involved, even repeatedly, in a succession of attacks - feature common for Mycobacterium tuberculosis14: One cutaneous manifestation both SLE and MS. of M. tuberculosis infection is ‘lupus vulgaris’, the nomenclature suggesting that the two diseases have RENAL INVOLVEMENT IN CLINICAL SYNDROMES CLOSELY historically shared similarities in their dermatological RELATED TO S.L.E. manifestations. All rheumatologic mimickers, drug-induced lupus, Wegener’s granulomatosis, microscopic polyangiitis, Churg-Strauss Visceral leishmaniasis15: Visceral leishmaniasis can present syndrome, Henoch-Schonlein purpura, anti-GBM vasculitis with fever, splenomegaly, pancytopenia, hypergamma- and sometimes polyarteritis nodosa may mimic renal globulinemia, and autoantibody (ANA) production. These manifestation of SLE. Renal thrombotic microangiopathy features may mimic SLE, but massive firm splenomegaly, very may also mimic active SLE nephritis. high acute phase reactants, and activation of coagulation system with high D-dimers point toward infection. CARDIOPULMONARY MIMICKERS Dermatomyositis, infections particularly endocarditis, Sarcoidosis16: It is an immunological mimicker of SLE. lymphomas, thrombotic , immune Positive ANA is reported in association with sarcoidosis in up thrombocytopenic purpura, Still’s disease, and sarcoidosis to 33% of patients during the acute phase, but antibodies and other connective tissue disorders may simulate to double-stranded DNA have not been reported. Fever, cardiopulmonary manifestations as well as few systemic arthritis, mouth ulceration, and pleuropericarditis have manifestations of SLE. Toxoplasma pericarditis may also all been described, both in early and in active chronic mimic systemic lupus erythematosus 18. sarcoidosis, together with non-specific rashes - all mimicking SLE. ENDOCRINOLOGICAL MIMICKER19 Seventy-five percent to 90% of patients with Graves’ disease SEROLOGICAL MIMICKERS and a smaller percentage of patients with Hashimoto’s Anti-nuclear antibody (ANA) is highly sensitive for diagnosing thyroiditis have antinuclear antibodies, and many have SLE and it is present in > 95% of cases of SLE. But, several anti-DNA antibodies as well, despite the fact that overt other connective tissue disorders and non-rheumatic SLE is uncommon. diseases, which show positivity to ANA, may mimic SLE. Most important condition is drug-induced lupus. CONCLUSION Though SLE is considered as “great imitator of many diseases”, Drug-induced lupus (DIL): DIL should be suspected in fortunately there are few conditions which simulate SLE in patients who do not have a diagnosis or history of SLE, who its dermatological or systemic manifestations. A rational Medicine Update-2011 297 approach including good history taking, clever physical biopsy often points to the correct diagnosis. examinations and targeted serological tests and target organ

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