Clinicopathologic challenge
A woman with night sweats, arthritis, and two distinct eruptions Gelareh Homayounfar1, MD, Mary J. Zimarowski2, MD, and Susan Burgin3, MD
1 Harvard Medical School, Boston, MA, USA, Departments of 2Pathology, 3 Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
What is your diagnosis?
Correspondence Susan Burgin, MD Department of Dermatology Beth Israel Deaconess Medical Center 330 Brookline Avenue Boston MA 02215 USA E-mail: [email protected] Conflicts of interest: None.
(a)
History A 44-year-old Caucasian woman presented to the dermatology clinic with a 3-week history of a pruritic eruption affecting her neck. On further questioning, the patient reported fatigue, myalgias, decreased appetite, drenching night sweats, and joint pain affecting her bilateral wrists and hands over the preceding few months. Her medications included ibuprofen and loratadine, which temporarily relieved the joint pain and pruritus, respectively. On physical examination, the patient was found to be afebrile. On her upper back and posterior neck, linear arrays of excoriated brown and red papules were seen (Fig. 1a). A wispy, blanching reticulate eruption of salmon-pink macules on the thighs was noted incidentally (Fig. 1b). Cervical lymphadenopathy and fullness of the bilateral wrist joints were found. Laboratory results were notable for the absence of leukocytosis and an elevated erythrocyte sedimentation rate (69 mm/h; normal: < 25 mm/h), C-reactive protein (43.1 mg/l; normal: < 8 mg/l), and ferritin (689 ng/ml; normal range: 10–200 ng/ml). The results of liver function tests were within normal limits. Tests for antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibody were negative. Parvovirus B19 immunoglobulin M (IgM) titers were normal. ª 2014 The International Society of Dermatology
(b) Figure 1 Physical examination in a 44-year-old woman revealed (a) linear arrays of excoriated brown and red papules on the patient’s upper back and posterior neck, and (b) a wispy, blanching, reticulate eruption of salmon-pink macules on her thighs
(a)
(b)
Figure 2 Histopathology shows (a) superficial dermal inflammation, superficial epidermal dyskeratosis, and dyskeratosis within the stratum corneum in a biopsy taken from the patient’s back, and (b) dermal edema, mixed cell inflammation with numerous neutrophils, rare eosinophils and intravascular neutrophils in a biopsy from the thigh. (Hematoxylin and eosin stain; original magnification [a] 9200, [b] 9400) International Journal of Dermatology 2015, 54, 865–867
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Clinicopathologic challenge
Homayounfar et al.
Night sweats, arthritis, and skin eruptions
Histopathologic examination of a punch biopsy from the upper back revealed mild spongiosis and dyskeratosis within the superficial epidermis and dyskeratosis within the stratum corneum (Fig. 2a). Additionally, a superficial perivascular mixed cell infiltrate with neutrophils and some eosinophils was seen. Histopathologic examination of a punch biopsy from the thigh revealed mild superficial and mid-dermal perivascular and interstitial mixed cell inflammatory infiltrate with numerous neutrophils and dermal edema (Fig. 2b). No granulomas were identified in either specimen, and special stains were negative for fungi and bacteria. Our patient was initially treated with ibuprofen 600 mg three times per day and omeprazole at night. She later reduced her ibuprofen dose and obtained substantial improvement of her night sweats, arthralgia, and rash. Unfortunately, several months later, she experienced the recurrence of arthralgia and treatment with hydroxychloroquine was recommended. However, the patient did not pursue this treatment and her symptoms resolved. Diagnosis Adult-onset Still’s disease (AOSD). Discussion Adult-onset Still’s disease is an idiopathic, multi-system, inflammatory disease characterized by a classic salmon-pink evanescent macular rash coinciding with spiking fever, arthritis or arthralgia, leukocytosis, lymphadenopathy, splenomegaly, liver dysfunction, sore throat, and the absence of rheumatoid factor and antinuclear antibody.1 Bywaters first described AOSD in 1971 in a case series of adult women with a clinical presentation identical to that in children with systemic juvenile idiopathic arthritis or Still’s disease.2 Adult-onset Still’s disease is a rare disorder, with an incidence of 0.16 per 100,000.3 It affects men and women equally, and the mean age of patients at presentation is 36 years.3 The diagnosis of AOSD depends on the exclusion of infectious, neoplastic, and autoimmune etiologies. The typical rash that accompanies AOSD consists of evanescent, non-pruritic salmon-pink macules and papules on the trunk and proximal extremities (as seen on our patients thighs) and facial involvement in some cases.4–6 This eruption typically presents during febrile episodes and may exhibit the Koebner phenomenon.4–6 In addition to this classically described eruption, more recent reports have cited chronic, pruritic, persistent papules and plaques, as were seen on our patient’s upper back and posterior neck, in 15–65% of patients with AOSD.7,8 A linear or flagellate configuration is the norm in these cases. Although this eruption has been described as flagellate erythema International Journal of Dermatology 2015, 54, 865–867
(placing it in the differential diagnosis that includes dermatomyositis, bleomycin toxicity, and shittake mushroom dermatitis), a review of the cases reported shows that flagellate cases more commonly involve scaly papules than macular erythema.9 The morphology of the two aforementioned eruptions of AOSD may provide insight into the chronicity and severity of the disease, and the concurrence of both eruptions is a notable feature of the present case.8 The classic evanescent eruption typically occurs early in the course of disease.4 Although some authors have noted the onset of persistent papules in the initial stages of AOSD, others have described papules that appear weeks after disease onset.7,8 The concurrence of the two eruptions, as seen in the present patient, is therefore possible and in fact one report described overlap in nine of 11 patients in one series.8 Additionally, although the presence of persistent papules has been reported to correlate with more severe disease requiring systemic corticosteroid therapy or steroid-sparing immunomodulatory therapy,7–9 our patient’s disease course was self-limiting, which underscores the heterogeneity of this rare disease. Histopathologically, the typical Still’s eruption consists of mild perivascular inflammation of the superficial dermis, with neutrophils, lymphocytes and histiocytes, vascular dilation, and dermal edema.4,7 The findings are somewhat similar to those observed in urticaria. Superficial dyskeratosis, with necrotic keratinocytes in the upper half of the epidermis and stratum corneum, is an unusual finding described in the persistent papules of AOSD.8 The dermal infiltrate in these persistent papules shows a mixture of neutrophils with scattered eosinophils, as observed in the present case. The course of AOSD can be self-limiting, polycyclic with complete remission between flares, or chronic, with a predominance of articular symptoms potentially resulting in joint destruction.10 The wrists, which were affected in our patient, and ankles are the most commonly involved joints.6 Only 7–24% of patients with AOSD respond to oral nonsteroidal anti-inflammatory drugs alone, and most require corticosteroids, disease-modifying anti-rheumatic drugs, or biologics to control the systemic and articular disease.4,6,10 Growing awareness of the distinct manifestations of AOSD may facilitate its diagnosis and assist in the clarification of the clinical implications of each of its cutaneous eruptions. References 1 Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of adult Stills disease. J Rheumatol 1992; 19: 424–430. 2 Bywaters EG. Stills disease in the adult. Ann Rheum Dis 1971; 30: 121–133. ª 2014 The International Society of Dermatology
Homayounfar et al.
3 Magadur-Joly G, Billaud E, Barrier JH, et al. Epidemiology of adult Stills disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis 1995; 54: 587–590. 4 Pouchot J, Sampalis JS, Beaudet F, et al. Adult Stills disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 1991; 70: 118–136. 5 van de Putte LB, Wouters JM. Adult-onset Stills disease. Baillieres Clin Rheumatol 1991; 5: 263–275. 6 Kontzias A, Efthimiou P. Adult-onset Stills disease: pathogenesis, clinical manifestations and therapeutic advances. Drugs 2008; 68: 319–337.
ª 2014 The International Society of Dermatology
Night sweats, arthritis, and skin eruptions
Clinicopathologic challenge
7 Suzuki K, Kimura Y, Aoki M, et al. Persistent plaques and linear pigmentation in adult-onset Stills disease. Dermatology 2001; 202: 333–335. 8 Lee JY, Yang CC, Hsu MM. Histopathology of persistent papules and plaques in adult-onset Stills disease. J Am Acad Dermatol 2005; 52: 1003–1008. 9 Ciliberto H, Kumar MG, Musiek A. Flagellate erythema in a patient with fever. JAMA Dermatol 2013; 149: 1425–1426. 10 Pouchot J, Arlet JB. Biological treatment in adult-onset Stills disease. Best Pract Res Clin Rheumatol 2012; 26: 477–487.
International Journal of Dermatology 2015, 54, 865–867
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A woman with night sweats, arthritis, and two distinct eruptions Gelareh Homayounfar1, MD, Mary J. Zimarowski2, MD, and Susan Burgin3, MD
1 Harvard Medical School, Boston, MA, USA, Departments of 2Pathology, 3 Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
What is your diagnosis?
Correspondence Susan Burgin, MD Department of Dermatology Beth Israel Deaconess Medical Center 330 Brookline Avenue Boston MA 02215 USA E-mail: [email protected] Conflicts of interest: None.
(a)
History A 44-year-old Caucasian woman presented to the dermatology clinic with a 3-week history of a pruritic eruption affecting her neck. On further questioning, the patient reported fatigue, myalgias, decreased appetite, drenching night sweats, and joint pain affecting her bilateral wrists and hands over the preceding few months. Her medications included ibuprofen and loratadine, which temporarily relieved the joint pain and pruritus, respectively. On physical examination, the patient was found to be afebrile. On her upper back and posterior neck, linear arrays of excoriated brown and red papules were seen (Fig. 1a). A wispy, blanching reticulate eruption of salmon-pink macules on the thighs was noted incidentally (Fig. 1b). Cervical lymphadenopathy and fullness of the bilateral wrist joints were found. Laboratory results were notable for the absence of leukocytosis and an elevated erythrocyte sedimentation rate (69 mm/h; normal: < 25 mm/h), C-reactive protein (43.1 mg/l; normal: < 8 mg/l), and ferritin (689 ng/ml; normal range: 10–200 ng/ml). The results of liver function tests were within normal limits. Tests for antinuclear antibody, rheumatoid factor, and anti-cyclic citrullinated peptide antibody were negative. Parvovirus B19 immunoglobulin M (IgM) titers were normal. ª 2014 The International Society of Dermatology
(b) Figure 1 Physical examination in a 44-year-old woman revealed (a) linear arrays of excoriated brown and red papules on the patient’s upper back and posterior neck, and (b) a wispy, blanching, reticulate eruption of salmon-pink macules on her thighs
(a)
(b)
Figure 2 Histopathology shows (a) superficial dermal inflammation, superficial epidermal dyskeratosis, and dyskeratosis within the stratum corneum in a biopsy taken from the patient’s back, and (b) dermal edema, mixed cell inflammation with numerous neutrophils, rare eosinophils and intravascular neutrophils in a biopsy from the thigh. (Hematoxylin and eosin stain; original magnification [a] 9200, [b] 9400) International Journal of Dermatology 2015, 54, 865–867
865
866
Clinicopathologic challenge
Homayounfar et al.
Night sweats, arthritis, and skin eruptions
Histopathologic examination of a punch biopsy from the upper back revealed mild spongiosis and dyskeratosis within the superficial epidermis and dyskeratosis within the stratum corneum (Fig. 2a). Additionally, a superficial perivascular mixed cell infiltrate with neutrophils and some eosinophils was seen. Histopathologic examination of a punch biopsy from the thigh revealed mild superficial and mid-dermal perivascular and interstitial mixed cell inflammatory infiltrate with numerous neutrophils and dermal edema (Fig. 2b). No granulomas were identified in either specimen, and special stains were negative for fungi and bacteria. Our patient was initially treated with ibuprofen 600 mg three times per day and omeprazole at night. She later reduced her ibuprofen dose and obtained substantial improvement of her night sweats, arthralgia, and rash. Unfortunately, several months later, she experienced the recurrence of arthralgia and treatment with hydroxychloroquine was recommended. However, the patient did not pursue this treatment and her symptoms resolved. Diagnosis Adult-onset Still’s disease (AOSD). Discussion Adult-onset Still’s disease is an idiopathic, multi-system, inflammatory disease characterized by a classic salmon-pink evanescent macular rash coinciding with spiking fever, arthritis or arthralgia, leukocytosis, lymphadenopathy, splenomegaly, liver dysfunction, sore throat, and the absence of rheumatoid factor and antinuclear antibody.1 Bywaters first described AOSD in 1971 in a case series of adult women with a clinical presentation identical to that in children with systemic juvenile idiopathic arthritis or Still’s disease.2 Adult-onset Still’s disease is a rare disorder, with an incidence of 0.16 per 100,000.3 It affects men and women equally, and the mean age of patients at presentation is 36 years.3 The diagnosis of AOSD depends on the exclusion of infectious, neoplastic, and autoimmune etiologies. The typical rash that accompanies AOSD consists of evanescent, non-pruritic salmon-pink macules and papules on the trunk and proximal extremities (as seen on our patients thighs) and facial involvement in some cases.4–6 This eruption typically presents during febrile episodes and may exhibit the Koebner phenomenon.4–6 In addition to this classically described eruption, more recent reports have cited chronic, pruritic, persistent papules and plaques, as were seen on our patient’s upper back and posterior neck, in 15–65% of patients with AOSD.7,8 A linear or flagellate configuration is the norm in these cases. Although this eruption has been described as flagellate erythema International Journal of Dermatology 2015, 54, 865–867
(placing it in the differential diagnosis that includes dermatomyositis, bleomycin toxicity, and shittake mushroom dermatitis), a review of the cases reported shows that flagellate cases more commonly involve scaly papules than macular erythema.9 The morphology of the two aforementioned eruptions of AOSD may provide insight into the chronicity and severity of the disease, and the concurrence of both eruptions is a notable feature of the present case.8 The classic evanescent eruption typically occurs early in the course of disease.4 Although some authors have noted the onset of persistent papules in the initial stages of AOSD, others have described papules that appear weeks after disease onset.7,8 The concurrence of the two eruptions, as seen in the present patient, is therefore possible and in fact one report described overlap in nine of 11 patients in one series.8 Additionally, although the presence of persistent papules has been reported to correlate with more severe disease requiring systemic corticosteroid therapy or steroid-sparing immunomodulatory therapy,7–9 our patient’s disease course was self-limiting, which underscores the heterogeneity of this rare disease. Histopathologically, the typical Still’s eruption consists of mild perivascular inflammation of the superficial dermis, with neutrophils, lymphocytes and histiocytes, vascular dilation, and dermal edema.4,7 The findings are somewhat similar to those observed in urticaria. Superficial dyskeratosis, with necrotic keratinocytes in the upper half of the epidermis and stratum corneum, is an unusual finding described in the persistent papules of AOSD.8 The dermal infiltrate in these persistent papules shows a mixture of neutrophils with scattered eosinophils, as observed in the present case. The course of AOSD can be self-limiting, polycyclic with complete remission between flares, or chronic, with a predominance of articular symptoms potentially resulting in joint destruction.10 The wrists, which were affected in our patient, and ankles are the most commonly involved joints.6 Only 7–24% of patients with AOSD respond to oral nonsteroidal anti-inflammatory drugs alone, and most require corticosteroids, disease-modifying anti-rheumatic drugs, or biologics to control the systemic and articular disease.4,6,10 Growing awareness of the distinct manifestations of AOSD may facilitate its diagnosis and assist in the clarification of the clinical implications of each of its cutaneous eruptions. References 1 Yamaguchi M, Ohta A, Tsunematsu T, et al. Preliminary criteria for classification of adult Stills disease. J Rheumatol 1992; 19: 424–430. 2 Bywaters EG. Stills disease in the adult. Ann Rheum Dis 1971; 30: 121–133. ª 2014 The International Society of Dermatology
Homayounfar et al.
3 Magadur-Joly G, Billaud E, Barrier JH, et al. Epidemiology of adult Stills disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis 1995; 54: 587–590. 4 Pouchot J, Sampalis JS, Beaudet F, et al. Adult Stills disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore) 1991; 70: 118–136. 5 van de Putte LB, Wouters JM. Adult-onset Stills disease. Baillieres Clin Rheumatol 1991; 5: 263–275. 6 Kontzias A, Efthimiou P. Adult-onset Stills disease: pathogenesis, clinical manifestations and therapeutic advances. Drugs 2008; 68: 319–337.
ª 2014 The International Society of Dermatology
Night sweats, arthritis, and skin eruptions
Clinicopathologic challenge
7 Suzuki K, Kimura Y, Aoki M, et al. Persistent plaques and linear pigmentation in adult-onset Stills disease. Dermatology 2001; 202: 333–335. 8 Lee JY, Yang CC, Hsu MM. Histopathology of persistent papules and plaques in adult-onset Stills disease. J Am Acad Dermatol 2005; 52: 1003–1008. 9 Ciliberto H, Kumar MG, Musiek A. Flagellate erythema in a patient with fever. JAMA Dermatol 2013; 149: 1425–1426. 10 Pouchot J, Arlet JB. Biological treatment in adult-onset Stills disease. Best Pract Res Clin Rheumatol 2012; 26: 477–487.
International Journal of Dermatology 2015, 54, 865–867
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