13 minute read
Dermatologic Look-Alikes
Erythematous Indurated Plaques
SIDRA DEEN; BRIANA FERNANDEZ; TARA L. BRAUN, MD
CASE #1
A 32-year-old Black woman presents with a severalmonth history of tender red lesions. She has had no prior illnesses, has no history of similar lesions, and takes no medications. The patient notes that the lesions started to appear on her upper thigh and spread to her chest and arms. She has recently felt fatigued and experienced some joint pain but is otherwise feeling well. On examination, erythematous indurated plaques are found on her left upper chest and right proximal arm. On the left thigh, an older lesion that progressed to a slightly hyperpigmented patch with subcutaneous atrophy is found.
CASE #2
A 15-year-old otherwise healthy girl presents with a 5-month history of a progressive rash. The lesions began on her lower legs and spread to her trunk. Other than the rash, the patient reports that she is otherwise feeling well. She tried over-the-counter topical steroids on the rash with minimal improvement. On physical examination, scattered erythematous to violaceous plaques are found on her legs, dorsal feet, and abdomen. An older lesion on her right dorsal foot shows a central indurated yellow-white sclerotic plaque with an erythematous to violaceous border.
Dermatologic Look-Alikes
CASE #1 Lupus Profundus
Lupus profundus, also known as lupus erythematosus panniculitis, occurs in 1% to 3% of patients with cutaneous lupus erythematosus (LE).1-5 Lupus profundus may occur in patients with concurrent systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE), or may manifest as an isolated incident lacking other cutaneous or systemic findings.1,2 Kaposi first described lupus profundus in patients with LE in 1883, and the disease was coined lupus erythematosus of Kaposi-Irgang by Arnold in 1956.1,3,5,6
Lupus profundus could serve as a precursor or signify recurrence in patients diagnosed with systemic lupus erythematosus.1-3 Of patients diagnosed with lupus profundus, 3% to 30% have SLE and these patients tend to have mild systemic involvement, though cases of severe systemic involvement have been reported.2 Discoid lupus erythematosus is also strongly associated with lupus profundus, with 70% of patients with lupus profundus displaying discoid lesions.4,7 Lupus profundus occurs twice as often in women as in men, mainly affecting women between 20 and 60 years of age.2,4,5 Cases in children younger than 12 years of age are rare.6
The etiology of lupus profundus is not completely understood due to the lack of specific research on its pathogenesis, though immune complex disease may play a role as indicated by the association with multiorgan disease and deep local lesional morphology.2 Recurrent lupus profundus may be associated with SLE, diabetes mellitus, glomerulonephritis, tuberculosis, and prior trauma to the area.3,4
Lesions from lupus profundus present as well-defined, erythematous, tender, indurated plaques, and subcutaneous nodules.1-3,6 Some lesions may develop overlying ulcerations or drainage. Discoid lupus erythematosus lesions may arise within lupus profundus lesions or elsewhere on the body.2,3 Discoid lupus erythematosus lesions present with a discoid plaque with scale that heals with scarring, follicular plugging, and atrophy.7 Lesions of lupus profundus are most commonly found on the face, breasts, trunk, buttocks, and proximal extremities, and lipoatrophy of the shoulders is characteristic of the disease.2,4,5 Healed lupus profundus nodules appear atrophic and hyperpigmented.3,5,6 Some patients with lupus profundus experience severe pain associated with active lesions, extensive cutaneous involvement causing disfigurement, major depression secondary to their skin disease and disfigurement, chronic fatigue, headaches, and severe comorbidities in those with systemic involvement.2
Diagnosis is made via clinical and histologic findings. Excisional wedge biopsies may be needed to adequately analyze the subcutis.5 Histologic analysis reveals lobular lymphocytic panniculitis.6,7 Lymphoid follicles with germinal centers are present in 50% of cases.5 Lymphoplasmacytic infiltrate may have lymphocytic nuclear dust, which is another clue in the diagnosis of lupus profundus as this is not common in other forms of panniculitis.1,6,8 Another characteristic feature is hyaline sclerosis of fat lobules with some extension into interlobular septae.2 Occasional histologic features include mucin deposits, lymphocytic vasculitis, granulomatous reactions, eosinophils, calcification, and overlying features of DLE (epidermal atrophy, interface change, superficial, and deep perivascular and periadnexal inflammation, basement membrane thickening, and increased dermal mucin).1,3,4
Though laboratory tests may be normal, lupus profundus may be associated with several abnormalities including positive antinuclear antibody (ANA) and/or lupus band test, hypocomplementemia, leukopenia, rheumatoid factor, increased erythrocyte sedimentation rate, and false-positive syphilis serology.1-3
Diseases that may mimic lupus profundus include poststeroid panniculitis, cold panniculitis, pancreatic panniculitis, erythema induratum, erythema nodosum, morphea profunda, WeberChristian disease, and subcutaneous panniculitis-like T-cell lymphoma (SPTCL).1,3,5 The histologic finding of lymphoid follicles in subcutaneous fat can be seen in erythema nodosum, morphea, erythema induratum, and panniculitis associated with dermatitis.1 Lupus profundus can be almost indistinguishable from SPTCL clinically; however, the diseases have unique
Oral hydroxychloroquine, quinacrine, or chloroquine are first-line treatments for lupus profundus in most patients.
histological and T-cell rearrangement and immunohistochemical studies can be used to differentiate the diagnoses.1,5,8 A helpful histologic clue that points towards SPTCL is rimming of atypical cells around fat droplets, though this feature has also been seen rarely in cases of lupus profundus.5 Lupus profundus appears most like morphea profunda in the later stages and can also be histologically similar; thus, careful clinical, histologic, and laboratory evaluation is needed to determine the diagnosis.5 First-line treatment for most patients with lupus profundus is oral antimalarials such as hydroxychloroquine, quinacrine, and chloroquine.2,3,5,6 Some patients may need to be treated
with a combination of antimalarials if they do not respond to monotherapy.2,4,6 Systemic glucocorticoids should only be used for resistant and disseminated lesions.4 Intralesional corticosteroids should be avoided as they usually have little effect and can exacerbate nodules. Some success has been seen in treatment with azathioprine, dapsone, cyclosporine, mycophenolate mofetil, or thalidomide. If all other therapies fail, surgical removal or debridement may be an option.4,5
The patient in this case was diagnosed with lupus profundus via punch biopsy; on further laboratory evaluation, she had elevated ANA titer and met diagnostic criteria for SLE. She was started on hydroxychloroquine, which is improving her cutaneous and systemic symptoms. supported by the higher levels of interleukin (IL)-4 cytokine and cell adhesion molecules detected in these patients.11,13 Increased reports of autoimmune diseases in both children and adults with morphea have been documented with up to 2% to 5% of children and 30% of adults diagnosed with concomitant autoimmune disease.9 An autoimmune cause is further supported by the presence of positive autoantibody titers. Antinuclear antibody is detected in 20% to 80% of patients and antitopoisomerase II alpha antibody is detected in 76% of patients with morphea.9 An increased prevalence of single-stranded DNA antibodies, antihistone antibodies, and rheumatoid factor also are found.9 Trauma, radiation, infection, and medications are also thought to play important roles in the pathogenesis of morphea.9,11
Clinically, morphea presents with erythematous, inflamed, and ill-defined plaques that may be itchy and tender.9,13 With time, these lesions develop a white center surrounded by a violaceous border.9,13 Plaques are typically self-limited and resolve within a few years.13 Once the active stage subsides, patients may develop hyper- or hypopigmentation of the involved skin.9,13 Excess collagen deposition in lesions destroys the normal structures of the skin, resulting in hairless, anhidrotic plaques.13 In some cases, the lesions do not resolve and patients have ongoing symptoms.13 Of the 5 clinical subsets of morphea, plaque morphea is the most common in adults and linear morphea is the most common in children.9
On histology, morphea presents with a perivascular infiltrate of lymphocytes in the reticular dermis and swelling of the endothelial cells.9 Plasma cells are found in up to 75% of lesions.15 In the later stages of the disease, the collagen bundles of the reticular dermis become hypertrophied and extend into the subcutaneous fat, giving the appearance of “fat trapping” in the dermis.9 Loss of eccrine glands and blood vessels occurs.9 Morphea is typically diagnosed clinically, however, a skin biopsy extending into the subcutaneous fat may be needed to confirm the diagnosis. A positive antinuclear antibody, antihistone antibody, and single-stranded DNA antibody may be present in some patients, but there is little clinical utility for autoantibody testing.13,15 Peripheral eosinophilia and elevated inflammatory markers may also help to confirm the diagnosis.13,15 Imaging with magnetic resonance imaging and ultrasonography may be a useful adjunct to clinical examination
CASE #2 Morphea
Morphea, also referred to as localized scleroderma, is an autoimmune disease that results in fibrosis of the skin and underlying tissues.9,10 It causes sclerosis of tissues derived from the primitive mesoderm; on rare occasions, it may include the central nervous system when present on the face and head.9,10 Unlike systemic scleroderma, which includes the presence of sclerodactyly, Raynaud phenomenon, and internal organ involvement, localized scleroderma is confined to the skin, subcutaneous tissue, and bone.9 Five classifications of morphea were originally described by Peterson et al. These include plaque, generalized, bullous, linear, and deep morphea.9,11,12
The incidence of morphea has been reported as 0.4 to 2.7 per 100,000 people, with an equal prevalence of disease in children and adults.9 The mean age of presentation in children is between 2 and 14 years and in adults is in the mid-40s.9 An increased predominance is found in females with the ratio of affected females to males reported as roughly 2.5-5:1.9,12,13 Approximately 72.7% to 82% of patients diagnosed with morphea are reported to be White individuals.9,13
The etiology of morphea is unclear but it is thought to be due to a multifactorial process that ultimately results in an imbalance between collagen production and destruction.9,13 Genetic predisposition, autoimmune dysregulation, and environmental factors may play a role in its pathogenesis; HLA class II allele DRB1*04:04 and class I allele HLA-B*37 have the strongest association with morphea.13,14 Autoimmune dysregulation is Excess collagen deposition in the lesions destroys normal structures of the skin, resulting in hairless, anhidrotic plaques.
Dermatologic Look-Alikes
TABLE. Lupus Profundus vs Morphea
Lupus Profundus1-8
Dermatologic presentation • Well-defined, tender, indurated plaques • Subcutaneous nodules • Overlying skin may appear normal or show signs of ulceration, scarring, or lesions from DLE • Active stage, early: erythematous, inflamed, and ill-defined violaceous plaques • Active stage, late: plaques with a white sclerotic center surrounded by a violaceous border • Postinflammatory stage: hairless, anhidrotic plaques with hypo- or hyperpigmentation
Characteristic locations • Face • Breasts • Trunk • Buttocks • Proximal extremities, especially shoulders
Epidemiology • 1%-3% of cutaneous lupus erythematosus patients • Twice as often in women vs men • Mainly affects patients 20-60 years of age • Incidence of 0.4-2.7 per 100,000 people • Equal prevalence in children and adults • Mean age of presentation in children is 2-14 years • Mean age of presentation in adults is 45 years • 2.5-5 times more common in females vs males • More common in White patients
Potential risk factors • Systemic lupus erythematosus • Diabetes mellitus • Glomerulonephritis • Tuberculosis • Trauma
Morphea9-15
• Varies depending on subclassification but most often on the trunk
• Autoimmune disease • Trauma • Radiation • Infection • Medications
Etiology
Histology
Diagnosis • None confirmed • Immune complex disease may play a role • None confirmed • Genetics, autoimmune dysregulation, and environmental factors may play a role
• Lobular lymphocytic panniculitis • Lymphoid follicles with germinal centers present in 50% of cases • Lymphocytic nuclear dust in infiltrate • Hyaline sclerosis of fat lobules with some extension into interlobular septae • Occasional histologic features: mucin deposits, lymphocytic vasculitis, granulomatous reactions, eosinophils, calcification, and overlying features of DLE • Lymphocytic perivascular infiltrate in the reticular dermis • Swelling of the endothelial cells • Presence of plasma cells • Later stage with hypertrophy of collagen bundles in the reticular dermis, fat trapping, and loss of both eccrine glands and blood vessels
• History and physical examination • Excisional wedge or punch biopsies • Immunofluorescence • History and physical examination • Biopsy of the subcutaneous fat
Treatment
DLE, discoid lupus erythematosus • Low doses of antimalarials • Topical or systemic steroids • Systemic immunosuppressants • Azathioprine, dapsone, and thalidomide • Surgical debridement or excision • Topical, intralesional, or systemic steroids • Phototherapy with UV-A light • Methotrexate • Combination of above treatments in severe cases
to determine the depth of involvement.In the evaluation of morphea, it is important to consider a variety of conditions in the differential diagnosis including systemic sclerosis, radiation dermatitis, lipodermatosclerosis, lupus profundus, mycosis fungoides, and necrobiosis lipoidica.15 Systemic sclerosis cannot be differentiated from morphea by histopathology alone, so it is necessary to search for other examination clues in these patients. The presence of nail fold capillary changes and sclerodactyly suggests the diagnosis of systemic sclerosis.9 Lipodermatosclerosis may also be difficult to distinguish from morphea because of its overlapping clinical and diagnostic features. The presence of venous hypertension and involvement of the medial malleolus favor the diagnosis of lipodermatosclerosis.15 Lupus profundus also shares several clinical, laboratory, and histopathologic features with morphea, but can be differentiated by the lack of prominent sclerosis in the dermis and subcutaneous tissue.5
Once the diagnosis of morphea is confirmed, several different treatment options may be considered. For patients with superficial lesions, topical treatment with corticosteroids for 3 to 4 weeks is appropriate.13 Topical tacrolimus can also be used.13 For patients with more widespread lesions, phototherapy with UV-A light may be considered as it has better penetration than UV-B, but both are ineffective for morphea that involves the subcutaneous tissue, muscle, or bone.10,13 In cases where phototherapy is not available, high-potency topical corticosteroids, intralesional corticosteroids, or topical tacrolimus may be considered.13 Rapidly progressive disease requires systemic therapy with oral or intravenous corticosteroids or methotrexate.13 Methotrexate combined with systemic steroids is most effective for severe cases.10,13 Mycophenolate mofetil may be considered as an alternative to methotrexate.13
The prognosis of morphea is generally good, especially in cases with superficial lesions.13 Morphea that extends deeper into the bone may result in functional disability and joint contractures.13
The patient in this case was diagnosed with generalized morphea, which was confirmed via punch biopsy. Given the extensive involvement, she is currently being treated with systemic steroids and methotrexate. ■
Briana Fernandez and Sidra Deen are medical students at Baylor College of Medicine in Houston, Texas; Tara L. Braun, MD, is a dermatologist at Elite Dermatology in Houston, Texas.
References
1. Massone C, Kodama K, Salmhofer W, et al. Lupus erythematosus panniculitis (lupus profundus): clinical, histopathological, and molecular analysis of nine cases. J Cutan Pathol. 2005;32(6):396-404. 2. Grossberg E, Scherschun L, Fivenson DP. Lupus profundus: not a benign disease. Lupus. 2001;10(7):514-516. 3. Díaz-Jouanen E, DeHoratius RJ, Alarcón-Segovia D, Messner RP. Systemic lupus erythematosus presenting as panniculitis (lupus profundus). Ann Intern Med. 1975;82(3):376-9. 4. Strober BE. Lupus panniculitis (lupus profundus). Dermatol Online J. 2001;7(2):20. 5. Arps DP, Patel RM. Lupus profundus (panniculitis): a potential mimic of subcutaneous panniculitis-like T-cell lymphoma. Arch Pathol Lab Med. 201;137(9):1211-1215. 6. Fox JN, Klapman MH, Rowe L. Lupus profundus in children: treatment with hydroxychloroquine. J Am Acad Dermatol. 1987;16(4):839-844. 7. Wimmershoff MB, Hohenleutner U, Landthaler M. Discoid lupus erythematosus and lupus profundus in childhood: a report of two cases. Pediatr Dermatol. 2003;20(2):140-145. 8. Bosisio F, Boi S, Caputo V, et al. Lobular panniculitic infiltrates with overlapping histopathologic features of lupus panniculitis (lupus profundus) and subcutaneous T-cell lymphoma: a conceptual and practical dilemma. Am J Surg Pathol. 2015;39(2):206-211. 9. Fett N, Werth VP. Update on morphea: part I. Epidemiology, clinical presentation, and pathogenesis. J Am Acad Dermatol. 2011;64(2):217-228. 10. Fett N, Werth VP. Update on morphea: part II. Outcome measures and treatment. J Am Acad Dermatol. 2011;64(2):231-242. 11. Peterson LS, Nelson AM, Su WP. Classification of morphea (localized scleroderma). Mayo Clin Proc. 1995;70(11):1068-1076. 12. Mayes MD. Classification and epidemiology of scleroderma. Semin Cutan Med Surg. 1998;17(1):22-26. 13. Penmetsa GK, Sapra A. Morphea. In: StatPearls. StatPearls Publishing; August 8, 2022. 14. Jacobe H, Ahn C, Arnett FC, Reveille JD. Major histocompatibility complex class I and class II alleles may confer susceptibility to or protection against morphea: findings from the Morphea in Adults and Children cohort. Arthritis Rheumatol. 2014;66(11):3170-3177. 15. Florez-Pollack S, Kunzler E, Jacobe HT. Morphea: current concepts. Clin Dermatol. 2018;36(4):475-486.
Do you have a Clinical Pearl
that you would like to share with your colleagues? Please submit your pearl to:
