Erythematous scaling plaques — some with surrounding hyperpigmentation — in a woman with systemic lupus erythematosus.
Erythematous scaling papules and plaques in an HIV-positive man.
A 41-year-old HIV-positive man presents with complaints of a localized eruption on his bilateral palms. The eruption began one week earlier, and there was no associated pruritus or pain. The man had applied petroleum jelly to the lesions without significant improvement. No history of genital ulceration or any other rashes on the body were reported. On physical examination, erythematous scaling papules and plaques were appreciated on bilateral palms. The remainder of the physical exam was within normal limits./p>
A 35-year-old woman with a history of systemic lupus erythematosus (SLE) presented with lesions on her bilateral palms, present for five months. Similar lesions were noted on her face, ears and forearms. There was no associated pain or pruritus and no alleviating or aggravating factors. The woman was taking hydroxychloroquine (Plaquenil, Quineprox) for her SLE but had not received treatment for the current cutaneous eruption. Erythematous scaling plaques — some with surrounding hyperpigmentation — were noted on the cheeks, conchal bowls, forearms and palms.What Are Your Diagnoses?
CASE #1: SyphilisSyphilis is a sexually transmitted infection that dates back to the late 15th century. Theories as to the spread of syphilis can be debated but the true culprit cannot. It is now known that the pathogen Treponema pallidum...
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CASE #1: Syphilis
Syphilis is a sexually transmitted infection that dates back to the late 15th century. Theories as to the spread of syphilis can be debated but the true culprit cannot. It is now known that the pathogen Treponema pallidum is responsible for the infection. This pathogen was first isolated and identified in 1905 by Schaudinn and Hoffmann.1
The infection may be congenitally or sexually acquired and is a chronic, cutaneous, and systemic disease. Syphilis progresses through three stages: primary, secondary, and tertiary. T. pallidum penetrates the body’s main defenses through mucosal surfaces and abraded skin. Once inside the host, it will attach to cells, multiply within hours, and then spread to regional lymph nodes and internal organs. This spread marks the start of the incubation period, which can last 10 to 90 days. On average, primary syphilis develops three weeks after the initial infection with T. pallidum.
During the primary stage or up to six months after the primary lesions have healed, the onset of secondary syphilis occurs. Nearly every patient will develop secondary syphilis if not treated appropriately during the primary stage. During this time, T. pallidum undergoes hematogenous dissemination and multiplication. This stage is generally accompanied by fever, malaise, and enlargement of the lymph nodes. The tertiary stage is the final stage of syphilis and occurs in approximately one-third of untreated individuals.
Primary syphilis begins as a painless papule, that enlarges and develops into an ulcer (chancre) within a few days. During this stage, patients will often have enlarged regional lymph nodes. Untreated, the ulceration will heal within a few weeks.
Secondary syphilis most commonly presents with nonpruritic, generalized, papulosquamous lesions. Often, these lesions are seen on the palms and soles, which should alert the clinician to consider the diagnosis of syphilis. Patients may also present with annular plaques with central hyperpigmentation, mucosal ulcerations, anogenital condyloma lata, nonscarring moth-eaten alopecia, split papules at the oral commisures, and granulomatous nodules and plaques. Patients who present with disseminated lesions that resemble the primary chancre are given the diagnosis of malignant syphilis.
Secondary syphilis generally resolves within three to 12 weeks; however, nearly a quarter of patients will relapse. After lesions heal, the patient goes into an asymptomatic state known as the latency period, which can last for years and is defined as the period between the healing of the clinical lesions and the appearance of late manifestations.
During the latency period of syphilis, patients will display no clinical symptoms but will exhibit positive serologic reactivity to a rapid plasma regain (RPR) or venereal disease research laboratory (VDRL) assay, and/or a microhemagglutination assay for T. pallidum antibodies (MHA-TP) or fluorescent treponemal antibody absorbed (FTA-ABS) test. Tertiary syphilis may appear months or years after infection and can also have a range of presentations. Nearly half of all patients will present with arciform, erythematous eroded plaques with central scarring referred to as cutaneous gummas. Some patients also may go on to develop skeletal, cardiovascular, and/or neurologic manifestations.
During the primary stage of syphilis, the epidermis is ulcerated and a diffuse infiltrate of plasma cells, lymphocytes, and histiocytes can be appreciated. Endothelial swelling and proliferation can also be observed. During the secondary stage, the epidermis may appear hyperkeratotic or ulcerated, but most commonly is psoriasiform.2 A perivascular or lichenoid infiltrate of many plasma cells, histiocytes, and lymphocytes is present as well. A granulomatous infiltrate may be present in older lesions.
Tertiary syphilis will exhibit tuberculoid granulomas, often with plasma cells. The epidermis may appear normal, hyperplastic, or atrophic, and fibrosis has been noted in some lesions. T. pallidum may be detected using the Warthin-Starry stain during the primary and secondary stages; however, spirochetes are usually not easily identified during the tertiary stage.2,3
Because of its vast expanse of clinical manifestations, syphilis is known as the great imitator and therefore has an extensive list of differential diagnoses. Consider other causes of anogenital ulcerations when differentiating primary syphilis from genital herpes, genital trauma, Behcet’s disease, genital carcinoma, chancroid, and lymphogranuloma venereum.
Cutaneous lesions of secondary syphilis may be confused with pityriasis rosea, eczema, psoriasis, lichen planus, primary HIV infection, and drug eruption. Lesions on the hands and feet may be confused with psoriasis, eczema, and discoid lupus erythematosus. Finally, tertiary syphilis may resemble sarcoidosis, tumors, lupus vulgaris, mycosis fungoides, and fungal infections.
Penicillin G is still the treatment of choice for all stages of syphilis. The dose varies depending on the stage of the disease. Thus far, penicillin resistance to T. pallidum has not been detected. If a person is allergic to penicillin, a tetracycline may be used. Follow-up examinations are recommended at months 1, 3, 6, and 12 following antibiotic treatment of early syphilis, then every six months for two years. Patients with late syphilis should be followed for three years. Due to the sexually transmitted nature of this disease, many countries require documentation and notification of previous sexual partners.4
Given that this patient also had concurrent HIV infection, he was treated with benzathine (Bicillin) penicillin 2.4 million units intramuscular weekly for three doses. The rash resolved, and repeat serologic examination one month following antibiotic treatment was within normal limits. The patient will be followed for at least two years.
CASE #2: Discoid lupus erythematosus
Lupus erythematosus is a multisystem disorder that prominently involves the skin. In some, the cutaneous lesions also may serve as an indicator of underlying systemic disease. There are three major forms of cutaneous lupus. The first is acute cutaneous lupus erythematosus (ACLE), which is characterized by the classic malar erythema, or butterfly rash. ACLE is most commonly associated with underlying SLE.
The second variant is subacute cutaneous lupus erythematosus (SCLE), which is a photosensitive eruption that is longer-lasting than classic ACLE. Discoid lupus erythematosus (DLE) falls under the category of chronic cutaneous lupus, and these lesions are often long-lasting and scarring.
Cazenave was the first to describe and name lupus erythematosus in the mid-1800s.5 It was not until 1964 that Dubois categorized the disorder into a spectrum of disease ranging from cutaneous lesions to life-threatening internal disease. In 1981 and 1982, Weston and Sontheimer found that anti-Ro antibodies were associated with neonatal lupus and SCLE, respectively.6,7
Lupus erythematosus is an autoimmune disorder that is believed to have a genetic predisposition with an environmental activator.8 Some propose that in the appropriate context, an immune response to a foreign antigen may lead to a limited and then broader autoimmune response. Ultimately, this ends with tissue injury. Certain autoantibodies are associated with certain skin diseases. For example, antibodies to double-stranded DNA (dsDNA) are seen in those with ACLE and antibodies to Ro are seen in those with SCLE.
DLE is the most common type of cutaneous lupus and may involve the epidermis, upper dermis, and lower dermis. There is a much lower female-to-male ratio with discoid lupus (2:1) than with to systemic lupus (8:1). Lesions are most commonly found on the face, scalp, and ears, but may also be seen in a widespread distribution. It is unusual for DLE to be present below the neck without lesions also being present above the neck.9
Unlike other forms of lupus, there is no clear association between sun exposure and the development of DLE. Lesions may present with erythema, scaling, atrophy, dyspigmentation, and scarring. Active lesions may feel indurated due to the intense inflammatory infiltrate in both the superficial and deep dermis. Follicular plugging and alopecia are other common features. The dyspigmentation is most often characterized by hyperpigmentation of the periphery with central hypopigmentation.
Lesions on the palms and soles may be ulcerative or keratotic. Discoid lesions have potential for scarring and given enough time, most patients will develop disfiguring scars, which may impact their quality of life. The majority (90%-95%) of patients with DLE do not develop SLE. Those with widespread lesions may be at greater risk of systemic involvement.
There are different histologic patterns that correspond to the various forms of cutaneous lupus. This write-up will discuss only the histopathologic findings seen in DLE. There is often marked hyperkeratosis and follicular plugging of the epidermis. The dermal-epidermal basement membrane zone is visibly thickened and obscured due to liquefaction degeneration. The thickening may be more apparent on periodic acid Schiff-stained sections. A lymphohistiocytic infiltrate is seen in the superficial and deep dermis in both a perivascular and periadnexal distribution.
The differential diagnosis of early lesions of DLE may be confused with syphilis, Jessner’s lymphocytis infiltrate, polymorphous light eruption, lymphocytoma cutis, lymphoma cutis, granuloma faciale, and sarcoidosis. Palm and sole lesions may be mistaken for lichen planus or secondary syphilis, and the presence of classic DLE lesions above the neck may be helpful in ascertaining the correct diagnosis. Scalp and oral lesions must also be differentiated from lichen planus.
When evaluating a patient with DLE for the presence of systemic disease, a detailed history, physical examination, and certain blood and urine testing should be performed. Laboratory tests to include in the systemic lupus-screening panel include an antinuclear antibody (ANA) with profile (dsDNA, Sm), urinalysis, complete blood count with differential, chemistries, erythrocyte sedimentation rate, and complement levels (C3, C4). It is very rare for a patient with systemic lupus to have a negative ANA.
On the other hand, a positive ANA does not signify systemic lupus and may be positive in patients with cutaneous lesions or with other diseases, or in a subset of normal individuals. Refer to the American College of Rheumatology 1982 revised criteria for guidelines on the classification of SLE.10
High-potency topical or intralesional corticosteroids are the safest treatment for DLE. Discoid lupus is one of a very few instances in which it is safe to use a high-potency corticosteroid on the face (if lesions are present at that location). It is important to educate patients on the risks of corticosteroid therapy and to monitor the skin for any side effects. Sun protection is also a mainstay of treatment, and patients should use a broad-spectrum, high-SPF sunscreen. Because of the scarring nature of DLE, cosmetic cover-up may be the best treatment for patients with hyper- and hypopigmented lesions.
Antimalarial therapy is the gold standard. Hydroxychloroquine (Plaquenil, Quineprox) is most commonly used and is generally well-tolerated. The usual dose is 200 mg once or twice daily. Eye toxicity is unlikely if the maximum dose does not exceed 6.5 mg/kg ideal body weight. Chloroquine (Aralen) and quinacrine are alternatives. Quinacrine is often added to the regimen of hydroxychloroquine in those who are not responding. Individuals with an allergy to hydroxychloroquine may still take chloroquine.
The prognosis of patients with DLE is favorable; however, many experience scarring and disfigurement, leading to depression and isolation. These patients must be followed closely, as the treatment of early lesions may be preventive. Exacerbation is possible in the spring and summer due to increasing sun activity and exposure. During this time, patients must take the appropriate precautions and minimize sun exposure. Serious systemic disease rarely develops with DLE, but when it occurs, patients may need to seek consultation with an internist, a rheumatologist, and/or a nephrologist.
This patient had been evaluated previously by rheumatology and was already on hydroxychloroquine 200 mg b.i.d., given the known history of SLE. After evaluation by dermatology, she was additionally prescribed clobetasol 0.05% ointment to be used b.i.d. on bilateral palms. A few lesions of DLE on the face were treated with intralesional triamcinolone in a concentration of 4 mg/mL.
Kerri Robbins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
1. NR Krieg, JG Holt, eds. Bergey’s Manual of Systematic Bacteriology, Volume 1, Baltimore, Md.: Lippincott Williams & Wilkins; 1984:49-57.
2. RP Rapini. Practical Dermatopathology. Philadelphia, Pa.: Elsevier Mosby; 2005:165-168, 225-227.
3. Elder DE, Elenitsas R, Johnson BL, et al, eds. Lever’s Histopathology of the Skin. 10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:579-583.
4. Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55(RR-11):1-94. A
5. Cazenave PLA. Lupus erthemateux (erythema centrifuge). Ann Malad Peau Syph. 1851;3:297-299.
6. Franco HL, Weston WL, Peebles C, et al. Autoantibodies directed against sicca syndrome antigens in the neonatal lupus syndrome. J Am Acad Dermatol. 1981;4:67-72.
7. Sontheimer RD, Maddison PJ, Reichlin M, et al. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med. 1982;97:664-671.
8. Nath SK, Kilpatrick J, Harley JB. Genetics of human systemic lupus erythematosus: the emerging picture. Curr Opin Immunol. 2004;16:794-800.
9. Prystowsky SD, Herndon JH Jr, Gilliam JN. Chronic cutaneous lupus erythematosus (DLE)—a clinical and laboratory investigation of 80 patients. Medicine (Baltimore). 1976;55:183-191.
10. American College of Rheumatology. The 1982 revised criteria for classification of systemic lupus erythematosus.
All electronic documents accessed July 6, 2012.