Persistent pruritic papules and plaques associated with adult‐onset Still's disease: Report of six cases

Typical skin rash, which appears and disappears along with respective rise and fall of fever, is well‐known, and included as one of the major criteria of adult‐onset Still's disease (AOSD) (Yamaguchi's criteria). In addition, various skin lesions are occasionally observed in association with AOSD. Persistent pruritic eruptions present with some clinical features, such as urticarial erythema, flagellate erythema, erythematous, slightly scaly or crusted papules, and/or plaques on the trunk and extremities. These lesions show unique histological features such as dyskeratosis with a peculiar, distinctive distribution in the upper epidermis and cornified layers with focal hyperkeratosis. We describe herein six cases of AOSD, which presented with skin lesions of persistent pruritic papules and plaques. All six cases were female, and three of them were elderly women. The patients presented with linear erythematous streaks, scaly erythema, keratotic papules, infiltrative plaques and irregular coalesced erythemas. By contrast, histological features were characteristic, and dyskeratotic cells were found in the horny layers as well as in the upper layers of the epidermis. Persistent pruritic eruption is an important cutaneous sign for the diagnosis of AOSD.     

Oral mucosa lesions as atypical manifestation of adult-onset Still’s disease

Adult-onset Still’s disease is a systemic inflammatory disorder of unknown etiology, characterized by skin rash, spiking fever, arthralgias or arthritis, and leukocytosis. The typical skin rash is evanescent, salmon-pink, nonpruritic and maculopapular, predominantly on the extremities. It is considered one of the major Yamaguchi’s criteria in adult-onset Still’s disease. However, atypical skin lesions are also described. Here, a 61-year-old woman with sore throat, spiking fever, polyarthritis and evanescent salmon-pink nonpruritic maculopapular skin rash on the extremities was diagnosed with adult-onset Still’s disease. In addition, atypical brown macules on oral mucosa, localized on the inner lips and tongue were also observed. Biopsy revealed a neutrophilic infiltrate. Despite treatment and improvement of the adult-onset Still’s disease, the atypical oral mucosal lesions persisted.     

Refractory macrophage activation syndrome in the setting of adult‐onset Still disease with hemophagocytic lymphohistiocytosis detected on skin biopsy treated with canakinumab and tacrolimus

A 19‐year‐old Caucasian female with adult‐onset Still disease (AOSD) presented for evaluation of an acute clinical decompensation and atypical annular papules and plaques with purpura on the lower extremities. A punch biopsy demonstrated histiocytes with engulfed degenerated erythrocytes and lymphocytes, consistent with hemophagocytic lymphohistiocytosis (HLH). HLH, clinically referred to as macrophage activation syndrome, is a rare complication of AOSD and is life‐threatening. Relevant clinical, laboratory, and histologic features of this diagnosis are reviewed.     

Adult‐onset Still disease with peculiar persistent plaques and papules

Adult‐onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon‐pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27‐year‐old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.     

The evolution of histopathologic findings in adult Still disease

Adult Still disease is an inflammatory arthritis classically associated with daily spiking fevers, evanescent rash, organomegaly, lymphadenopathy, and laboratory anomalies. The typical cutaneous lesions are thin pink papules in a morbilliform distribution, of short duration. Histologically, these lesions are characterized by a superficial perivascular and interstitial mixed dermatitis with lymphocytes and variable neutrophils. A variant clinical presentation is increasingly recognized, which demonstrates persistent hyperpigmented plaques, often with a rippled or linear appearance. The histologic findings consist of upper epidermal dyskeratotic keratinocytes, increased dermal mucin, and a superficial perivascular infiltrate of lymphocytes and possibly neutrophils or eosinophils. We encountered 2 patients who presented with the characteristic rash of adult Still disease, both of whom progressed to develop the pigmented cutaneous plaques. We propose that this variant clinical and histologic appearance is the outcome of persistent disease activity.     

Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult‐onset and juvenile Still's disease

Background: ‘Persistent pruritic papules and plaques' of Still's disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult‐onset Still's disease. Methods: We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. Results: Our three patients each presented with clinical findings consistent with Still's disease. The youngest patient suffered from the juvenile form of Still's disease (systemic‐onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. Conclusions: These cases confirm the characteristic clinical and histopathologic findings of ‘persistent papules and plaques of Still's disease’ and show the potential for this eruption in both the adult and juvenile age groups. Fortna RR, Gudjonsson JE, Seidel G, DiCostanzo D, Jacobson M, Kopelman M, Patel RM. Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult‐onset and juvenile Still's disease.     

Clinical and histopathological features of cutaneous manifestations of adult‐onset Still disease

Adult‐onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon‐pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in 2 Asian women are highlighted accompanied by a relevant review of the disease.     

Persistent plaques and linear pigmentation in adult-onset Still's disease.

A 25-year-old Japanese man presented with high spiking fever, arthralgia and a skin rash. A pruritic edematous erythema with persistent plaques was found mainly on the trunk; these lesions persisted even when the fever subsided, with prominent linear pigmentation. As marked neutrophilia and a high level of serum ferritin were detected, a diagnosis of adult-onset Still's disease (AOSD) was made, even though the persistent eruption was not characteristic of the disease. Oral prednisolone, together with low-dose methotrexate, was given with good results. In the literature, a similar atypical rash has been reported in 11 cases in Japan. All of them required high-dose administration of corticosteroids or other immunosuppressive agents. Severe systemic complications were seen in 3 patients, and 2 cases died of the disease. Persistent plaques and linear pigmentation are some of the manifestations of AOSD, which cannot be overlooked. This appearance could be an indication that suggests an increased risk of systemic complications and a prolonged time to clinical remission.     

Adult-onset Still’s disease as a cutaneous marker of systemic disease

Adult-onset Still’s disease (AOSD) is a rare, systemic, inflammatory disorder characterized by spiking fevers, an evanescent eruption, arthritis, and multiorgan involvement. The disease has been recently classified as a polygenic autoinflammatory disorder at the “crossroads” of autoinflammatory and autoimmune diseases. The highly characteristic salmon-colored eruption is a cutaneous manifestation of a generalized inflammatory reaction and an important diagnostic criterion. In addition to the evanescent eruption, there are atypical persistent papules and plaques in many patients with AOSD. Emerging data suggest that AOSD with this typical evanescent eruption has a different clinicopathologic presentation and clinical course than AODS with atypical cutaneous manifestations.It appears that there are two subtypes of AOSD with different immunologic profiles, including (1) a systemic disease with high fever, organ involvement, and elevated levels of ferritin, and (2) a chronic disease course with arthritis as the predominant finding. These observations provide novel insight into the disease pathogenesis, suggesting that the underlying mechanisms might differ between these two forms, partially explaining the reported differences in drug response.Recent advances in the understanding of AOSD are summarized with a focus on the spectrum of cutaneous manifestations and its relationship to systemic inflammation.     

与成人Still病相关的皮肤表现

成人Still病是一种病因未明的系统性炎症性疾病,临床上以规律性发热、关节炎或关节痛、淋巴结肿大、肝脾肿大及皮疹为主要特征.现有诊断标准中,Yamaguchi标准具有较高的敏感性和特异性.皮肤受累为成人Still病的主要症状之一,典型的一过性皮疹为Yamaguchi标准的一项重要表现.非典型皮疹具有多形性,包括持久性丘疹,斑块、荨麻疹样、皮肌炎样皮疹等.持久性丘疹,斑块及荨麻疹样皮疹特征性的临床及病理表现有利于疾病早期诊断,而持久性丘疹,斑块与皮肌炎样皮疹可能与疾病严重程度、预后相关.     

Treatment of refractory adult‐onset pityriasis rubra pilaris with TNF‐alpha antagonists: a case series

Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.     

Health‐related quality of life among Darier’s disease patients

Background Darier’s disease (DD) is an autosomal dominant skin disorder characterized by persistent eruption of hyperkeratotic papules. The effect of DD on quality of life (QOL) has been assessed in only one study, which found no correlation between the Dermatology Life Quality Index (DLQI) score and clinical severity of the disease. The correlation between health‐related quality of life (HRQL) and other diseases and patient characteristics has not been studied. Objectives To examine the HRQL of patients with DD and to evaluate the association between HRQL scores and disease and patient characteristics. Methods A total of 74 DD patients completed three QOL questionnaires: DLQI, EQ‐5D, and one specially designed for the study. The data reported in this study were collected as part of a larger study on the clinical characteristics of DD; the socio‐demographic and clinical data were used in the statistical analysis of the current study. Results Mean DLQI was 5.41 ± 5.57 and the mean EQ‐Visual Analogue Scale (VAS), was 70.84 ± 19.25. DLQI and EQ‐VAS were significantly associated with skin area affected, disease severity, age at onset of DD and a seborrhoeic distribution pattern of DD. Stepwise linear regression showed skin area affected to be the most significant variable in the predication of DLQI (beta = 0.183; SE = 0.04; P < 0.001), and disease severity the most significant variable in the predication of EQ‐VAS (beta = ?9.15; SE = 3.21; P < 0.006). Conclusions Darier’s disease has a negative impact on HRQL of patients and the HRQL is associated with various disease characteristics, mainly skin area affected and clinical severity.     

Neutrophilic figurate erythema of infancy: A diagnostic challenge

Neutrophilic figurate erythema of infancy (NFEI) is a rare variant of annular erythema of infancy. It is characterized by annular erythematous plaques, occasionally with a polycyclic configuration. The main challenge is to differentiate this rare entity from other figurate erythemas associated with serious diseases such as neonatal lupus erythematosus. We present the case of a 9‐month‐old female admitted with a skin rash of unclear etiology. The rash started on her face at the age of 3 months and gradually spread to her extremities. She had no constitutional symptoms, and her health and development were otherwise unremarkable since birth. This persistent skin eruption consisted of many ill‐defined erythematous papules and annular plaques. Histologic examination revealed perivascular neutrophils and eosinophils with abundant nuclear dust without signs of vasculitis. NFEI is a diagnostic enigma both clinically and histologically. Absence of an underlying cause, dermal neutrophilic infiltrate with leukocytoclasis, and lack of vascular damage are the keys to diagnosis.     

Cutaneous plasmacytosis and multinucleate cell angiohistiocytoma‐like lesion in a patient with hepatitis B: A fortuitous triad?

A 28‐year‐old woman of Chinese descent, with congenital chronic hepatitis B presented with a 7‐year history of erythematous‐brown papules and plaques on her groins, axillae, and forehead. A first skin biopsy showed findings consistent with two concomitant, yet highly uncommon cutaneous diseases. The presence of lymphoid nodules with germinal centers and clustered polyclonal plasma cells was consistent with cutaneous plasmocytosis. Second, a diffuse proliferation of non‐atypical small vessels (CD31+, CD34+, and HHV8?) in a hypercellular stroma peppered with angulated giant cells (CD163+, CD68?) was suggestive of multinucleate cell angiohistiocytoma (MCAH). Interestingly, the second biopsy of a different plaque on the forehead showed only plasmacytosis and the clinical appearance of both plaques and papules alluded to the distinct presence of both concurrent entities. We speculate the immune modulating effects of chronic hepatitis B may have led to a polyclonal plasmacytic proliferation within the dermis. Furthermore, MCAH has been reported in conjunction with other inflammatory skin diseases such as hidradenitis suppurativa and as such we propose that the MCAH lesion in our case may have arisen as a secondary, reactive process to the cutaneous plasmacytosis.     

Papuloerythroderma‐like cutaneous involvement of a CD62L− subclone of T‐cell prolymphocytic leukemia

We report the case of an 88‐year‐old Japanese man with erythrodermic involvement of T‐cell prolymphocytic leukemia (T‐PLL). He had a history of pharyngeal diffuse large B‐cell lymphoma successfully treated with polychemotherapy including cyclophosphamide and epirubicin, 6 years before the current illness. He presented with numerous reddish, coalescing, flat‐topped papules on the trunk and extremities, sparing the skin folds of the abdomen, the features of which mimicked those of papuloerythroderma. Immunohistochemistry showed perivascular and epidermotropic infiltration of CD3⁺ CD4⁺ T cells in the cutaneous lesion. However, flow cytometric analysis revealed that the skin infiltrating T cells were negative for surface CD4, and that CD3⁺ CD4^? CD8^? cells made up 92% of the T‐cell fraction of peripheral blood. The circulating atypical T cells had a round or oval nucleus and prominent nucleoli, and the deletion of chromosomes 6q, 13 and 17. These cytological profiles were consistent with those of T‐PLL and distinct from those of Sézary cells. The same T‐cell clone was detected in the cutaneous lesion and peripheral blood, but the expression of CD62L was absent in the skin infiltrates and present in the circulating cells. No specific mutation was detected in STAT3 or STAT5B. Although low‐dose oral etoposide had a beneficial effect on the skin rash, a fatal crisis of marked leukocytosis (169 × 10³/μL) occurred 19 months after the illness onset. CD62L‐leukemic cells of T‐PLL may infiltrate the skin to form papuloerythroderma‐like cutaneous lesions.     

Leukemia cutis in acute lymphocytic leukemia masquerading as viral exanthem.

Leukemia cutis is a specific skin lesion caused by infiltration of leukemic cells into the skin. It is uncommon in acute lymphocytic leukemia (ALL). It typically manifests as red or violaceous papules, nodules, or plaques, mainly on the face. Leukemia cutis presenting with a generalized viral exanthem-like maculopapular eruption appears to be rare in the English literature. We report such a case. A 19 year-old man presented with a generalized purpuric maculopapular eruption of eight day's duration. Hematologic studies showed changes of acute lymphocytic leukemia, T-cell type. A skin biopsy specimen revealed a cuff-like, dense, perivascular infiltration of atypical lymphocytes in the upper and mid-dermis, consistent with leukemia cutis. The rash resolved in two weeks after chemotherapy. Our case illustrates that leukemia cutis should be considered in the differential diagnosis of a generalized morbilliform viral exanthem-like eruptions. Skin biopsy is important in establishing the diagnosis.     

A case of Wong‐type dermatomyositis treated with rituximab and IVIG

A 37‐year‐old woman presented to our rheumatology–dermatology clinic with a rash, muscle weakness and fatigue. She has had prior diagnoses of cutaneous lupus and lichen planus based on skin biopsies. She did not respond to topical steroids, hydroxychloroquine and dapsone. Clinically, she had sharply demarcated photo‐distributed erythema over the upper back, chest and upper arms, along with hyperkeratotic follicular papules on bilateral upper arms, shoulders, posterior neck, behind the ears, chest including breasts, abdomen and right buttock. Investigations revealed a high titre ANA, elevated creatinine kinase, aldolase and positive anti‐MJ/nuclear matrix protein 2 (NXP‐2). A skin biopsy showed findings of connective tissue disease. The diagnosis of Wong‐type dermatomyositis was made. She responded to therapy with mycophenolate mofetil, rituximab and IVIG.     

A Mimic of Self‐Healing Juvenile Cutaneous Mucinosis?

A 14‐year‐old boy presented with a chronic history of atypical papular mucinosis consisting of multiple subcutaneous nodules and confluent papular skin lesions. He initially presented at age 2 years with the rapid onset of numerous subcutaneous nodular lesions that completely resolved over a period of years. Clinical and histologic evidence, together with his clinical course, were suggestive of self‐healing juvenile cutaneous mucinosis (SHJCM), but a few years later, during childhood, he experienced a recurrence of the subcutaneous nodules involving the limbs, trunk, and face, in addition to new findings of multiple flesh‐colored papules coalescing into plaques on his neck and back. Although his early childhood course and histologic picture were suggestive of SHJCM, the progressive nature of his disorder is not like that seen in SHJCM and appears different from other reported disorders involving cutaneous mucinosis.     

Atypical cutaneous γδ T cell proliferation with morphologic features of lymphoma but with clinical features and course of PLEVA or lymphomatoid papulosis

Reactive lymphoid infiltrates of the skin composed predominantly of gamma‐delta (γδ) T cells are not well described in the literature. Herein we report a case of an otherwise healthy 4‐year‐old male who presented with a waxing and waning papular rash characterized by small, discrete crusted papules spread across his trunk, face and extremities. Clinical evaluation revealed no evidence of systemic disease. Microscopic examination revealed a dermal, perivascular infiltrate of highly atypical lymphocytes with a γδ T cell phenotype, worrisome for primary cutaneous γδ T cell lymphoma. The clinical course, however, was that of a reactive condition and prompted consideration of a diagnosis of pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP). In many ways, this case defies current classification schemes and seems to expand the spectrum of reactive γδ T cell infiltrates of the skin.