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Adult-Onset Still’s Disease with Dermatopathic Lymphadenitis Clinicopathologic Features: A Rare Case Report and Review of the Literature

Adult-Onset Still’s Disease with Dermatopathic Lymphadenitis Clinicopathologic Features: A Rare... Hindawi Case Reports in Immunology Volume 2022, Article ID 1653683, 5 pages https://doi.org/10.1155/2022/1653683 Case Report Adult-Onset Still’s Disease with Dermatopathic Lymphadenitis Clinicopathologic Features: A Rare Case Report and Review of the Literature 1,2 3 1,4 5 Reda A. Elhawary, Mir Nadeem , Mohammed S. Abdelwahed, Mansour Somaily, and Shahenda Y. Alemam Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Department of Pathology, Histopathology Consultant, Khamis Mushyte General Hospital, Khamis Mushait, Saudi Arabia Department of Medicine, King Khalid University and Associated Hospital, Abha, Saudi Arabia Department of Pathology, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia Department of Medicine, Rheumatology Division, King Khalid University Medical City, Abha, Saudi Arabia Department of Medicine, Rheumatology Division, Khamis Mushyte General Hospital, Khamis Mushait, Saudi Arabia Correspondence should be addressed to Mir Nadeem; mirnadeem44@gmail.com Received 10 February 2022; Accepted 18 May 2022; Published 3 June 2022 Academic Editor: Necil Ku¨t¨ukç¨uler Copyright © 2022 Reda A. Elhawary et al.  is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Adult-onset Still’s disease (AOSD) is an inŠammatory disorder characterized by fever, arthritis, and a transient skin rash. It is a rare condition characterized by inŠammatory multisystem changes of unknown cause. A 35-year-old woman was admitted to rheumatology department of tertiary care hospital complaining of painful wrist and skin rash as well as fever, generalized lymphadenopathy, weight loss, and fatigue.  e early diagnosis of AOSD was con“rmed by clinical history, examination, and laboratory tests, as well as a con“rmatory skin biopsy with typical histopathological features, namely, upper epidermal dys- keratosis and dermal inŠammatory neutrophilic in“ltration.  e patient’s condition was treated with steroids and NSAIDs, to which she responded well, and on follow-up, her symptoms regressed along with improvement in biochemical parameters.  e authors suggest that skin biopsy and con“rmation of histopathological diagnosis of AOSD are useful in the diagnosis and proper management of AOSD patients in cases with clinical suspicion of AOSD. untreated AOSD [3]. Still’s disease is named after the cli- 1. Introduction nician George Still, who “rst described it in children in 1896. Adult-onset Still’s disease (AOSD) is a rare inŠammatory In 1971, another clinician, Bywater, documented a similar disorder with a variety of clinical symptoms, including high- clinical presentation in 14 patients. Young adults are most grade fever, arthritis, a transient rash, lymphadenopathy, commonly a¢ected by the disease, which has a bimodal age distribution of 15–25 and 36–46 years [4]. Several classi“- and multiple organ involvement [1].  e annual incidence of AOSD has been estimated between 0.16 and 0.4 per 100,000 cation criteria have been proposed; however, the Yamaguchi people worldwide, with the reported prevalence rates from 1 criteria [5] are the most widely cited and provide the highest to 34 cases per 1 million people [2].  e incidence of AOSD sensitivity (93%) within these criteria, and the exclusion of remains low due to underdiagnosis of the condition and the other diseases is required. Fautrel et al. [6] proposed a new insidious nature of the disease. Macrophage activation set of criteria that added serum ferritin and glycosylated syndrome (MAS) and disseminated intravascular coagula- ferritin levels, but no exclusion criteria were included.  e tion (DIC) are two life-threatening consequences of sensitivity and speci“city of Fautrel criteria are 80.6% and 2 Case Reports in Immunology 98.5%, respectively. *e outcome of AOSD is unpredictable, performed, which revealed a preserved normal lymph node and the disease is conventionally divided into three different architecture, reactive lymphoid follicles, and marked para- cortical expansion with irregular pale areas (Figure 3) subtypes based on disease evolution: monophasic course, usually a single cyclic course, intermittent course, and, fi- consisting of numerous foamy histiocytes with brown nally, chronic course. *e condition in patients with melanin pigment, interdigitating dendritic cells, and monophasic course usually resolves within weeks to months Langerhans cells mixed with small lymphocytes. and regresses completely in less than a year [7]. Gluco- Eventually, the patient was diagnosed with adult-onset corticoids (GCs) commonly induce a dramatic clinical re- Still’s disease with associated dermatopathic lymphadenitis sponse, even within few hours and days; the higher dosages characterized as the monocyclic clinical pattern of AOSD. are reported as being more efficient than lower dosages *e patient was treated with anti-inflammatory drugs, a low leading to subsequent less relapses of the disease [8]. *e dose of the steroid methylprednisolone 1mg/kg for two reduction of concomitant glucocorticoids dosage following weeks, and nonsteroidal anti-inflammatory drugs (NSAIDs) treatment with the IL-1 receptor antagonist is seen in adult- were administered because of the active arthritis. *e patient improved after treatment, and upon two weekly follow-up onset Still’s disease [9]. Methotrexate and other disease- modifying antirheumatic drugs (DMARDs) are commonly for six months clinically, the patient had no fever, her ar- used to treat severe acute inflammatory synovitis [10]. In thritis improved, rash resolved, and ESR and C-reactive addition to DMARDs, biologic agents are used to treat protein (CRP) were negative. Clinically, there was no refractory AOSD, including TNF-α inhibitors (infliximab, lymphadenopathy with no further rheumatological etanercept) and IL-1 (anakinra, canakinumab) and IL-6 complaints. blockers (tocilizumab, sarilumab) [11]. 2.1. Ethical Declaration. *e case report was conducted in 2. Case Report full compliance with the Declaration of Helsinki and according to the research guidelines, and informed consent A 35-year-old woman presented to the rheumatology clinic was obtained from the patient for publication as a rare case of a tertiary care hospital in Aseer complaining of wrist report. Ethical approval from the institution was not needed pain and skin rash started 4 months ago. *e patient had for case report publication. accompanying symptoms such as weight loss, fatigue, in- ability to climb stairs, and inability to raise her arm above her head. *e patient had no significant past medical 3. Discussion history. On examination, the patient had polyarthritis with bilateral arthritis of the hand (metacarpophalangeal, in- George Still in 1896 recognized a clinical picture in children terphalangeal) and shoulder joints and a maculopapular that resembled polyarthritis in adults and named it Still’s erythematous rash affecting both extremities. After 2 days disease, which is the eponymous term for juvenile idiopathic of admission, the patient developed a fever which was high arthritis. In 1971, a number of adult patients were observed grade, and the maximum recorded temperature of 102.4 F to have features similar to children with juvenile arthritis occurred in the late afternoon. Laboratory investigations and did not meet the criteria for classic rheumatoid arthritis, revealed leukocytosis with TLC (16000/l), anemia (hae- so the term adult Still’s disease was coined to describe these moglobin 9 gm/dl), elevated ESR (50 mm/h) and C-reactive patients [6]. *e etiology of AOSD is unclear; however, protein (CRP 88mg/l), and serum ferritin (8000 ng/ml), genetic variables and various infectious triggers have been proposed as key etiologic features. However, confirmation of and CTscan of the thorax and abdomen and pelvis showed generalized lymphadenopathy without any significant in- an infectious etiology is still under investigation, and the fective focus with cervical lymphadenopathy largest one evidence for genetic components is inconclusive. *ere is measuring 2.3∗3.2 cm in left submandibular region also uncertainty regarding the presence of the same etiopatho- bulky bilateral axillary lymph nodes largest measuring genic factors among all the AOSD patients, and it has always 3.3∗2.3 cm along with mediastinal and para-aortic lymph been a cause of concern. Various pathogens, including vi- nodes. Rheumatoid factor (RF), anti-CCP, and antinuclear ruses and bacteria, have been studied to determine their antibody (ANA) tests were negative. *e differential di- involvement in the pathogenesis of AOSD. Bacterial path- agnoses in addition to AOSD, at the preliminary evalua- ogens include Yersinia enterocolitica and Mycoplasma tion, were mixed connective tissue disease, rheumatoid pneumonia [8]. Studies have been conducted on the im- arthritis, and psoriatic arthritis. munogenetics of AOSD, and a study on 62 French patients Punch biopsy of the skin was done in coordination with found an association between HLA-B17, -B18, -B35, and the dermatology department in day care, and it revealed -DR2 and AOSD. However, the study has not been validated epidermal dyskeratotic keratinocytes mainly in the upper by a larger investigation [9]. Fever, rash, sore throat, and layers of the epidermis and focally in the stratum corneum arthralgia are the common symptoms of AOSD [12]. Fever is (Figure 1). *ere was a superficial perivascular, periadnexal, usually above 39.0 C, and peak temperatures are observed in and interstitial inflammatory infiltrate rich in neutrophils the late afternoon and early evening [13]. *e normal rash in and few lymphocytes (Figure 2). *ese histologic features are AOSD is asymptomatic and defined as salmon-colored, consistent with Still’s disease in adults. To rule out the maculopapular eruptions affecting mainly the trunk and possibility of lymphoma, a lymph node biopsy was extremities. However, in active AOSD, an unusual, Case Reports in Immunology 3 Figure 1: Adult onset Still disease, skin biopsy with multiple individual dyskeratotic keratinocytes in the upper epidermal layers (thin arrows) and perivascular neutrophilic inflammatory infiltrate (thick arrow) (H&E X100). (a) (b) Figure 2: Adult onset Still disease, (A) skin biopsy with (a) multiple individual dyskeratotic keratinocytes in the upper epidermal layers (thin arrows) and (b) perivascular neutrophilic inflammatory infiltrate (thick arrow) (H&E X400). (a) (b) Figure 3: Dermatopathic lymphadenopathy. (a) Subcapsular nodular showing palely stained area in the paracortical region. Hyperplastic lymphoid follicles are also present (H&E X100). (b) Numerous pigment-containing histiocytes were present in the pale stained area (H&E X400). nonevanescent rash with pruritic, persistent papules or both important signs of AOSD and may be associated with plaques has been observed in addition to the conventional odynophagia [15]. Several cytokines, including tumor ne- rash [14]. Sore throat and an increase in serum ferritin are crosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-18, 4 Case Reports in Immunology have been associated with the pathophysiology of AOSD. Conflicts of Interest *e levels of these cytokines are extremely high in people *e authors declare that they have no conflicts of interest. with active AOSD [3]. *e knees, wrists, ankles, and elbows are affected. During febrile episodes, joint symptoms usually worsen [16]. References In our case, laboratory tests showed a high ESR (50) and leukocytosis (16000) with a preponderance of neutrophils. [1] K. S. Eardley, K. Raza, D. Adu, and R. D. Situnayake, “Gold treatment, nephrotic syndrome, and multi-organ failure in a AOSD is characterized by a disproportionately high serum patient with adult onset still’s disease,” Annals of the Rheu- ferritin level (6000). Hyperferritinemia affects approxi- matic Diseases, vol. 60, no. 1, pp. 4-5, 2001. mately 70% of patients and was previously considered to be [2] K. J. Evensen and H. C. Nossent, “Epidemiology and outcome due to cytokine production triggered by the reticuloendo- of adult-onset still’s disease in Northern Norway,” Scandi- thelial system or liver injury [17]. As in our diagnostic case navian Journal of Rheumatology, vol. 35, no. 1, pp. 48–51, report, rheumatoid factor and antinuclear antibodies were usually negative [18]. AOSD as a diagnosis of exclusion [3] R. Giacomelli, P. Ruscitti, and Y. Shoenfeld, “A compre- required a thorough examination including skin biopsy, hensive review on adult onset still’s disease,” Journal of Au- which was performed. Histopathologic examination of the toimmunity, vol. 93, pp. 24–36, 2018. rash in this case revealed dyskeratotic cells confined to the [4] M. Kurasawa, K. Kotani, G. Kurasawa, K. Shida, S. Yamada, and T. Tago, “Adult-onset still’s disease in a patient over 80 upper epidermis and stratum corneum, perivascular neu- years old successfully treated with low-dose methotrexate trophilic inflammatory infiltration of the upper dermis, and therapy,” Age and Ageing, vol. 36, no. 1, pp. 104–106, 2006. nuclear debris. *e specific histological features of the rash [5] M. Yamaguchi, A. Ohta, T. Tsunematsu et al., “Preliminary in AOSD patients have been documented in several pub- criteria for classification of adult still’s disease,” Journal of lications such as Cozzi et al. [19], with dyskeratosis confined Rheumatology, vol. 19, pp. 424–430, 1992. to the upper epidermis and stratum corneum serving as an [6] B. Fautrel, E. Zing, J.-L. Golmard et al., “Proposal for a new set important diagnostic marker, as explained by neutrophil and of classification criteria for adult-onset still disease,” Medicine, lymphohistiocytic infiltration of the upper dermis and vol. 81, no. 3, pp. 194–200, 2002. dermal mucin deposits are among the additional features. [7] E. G. Bywaters, “Still’s disease in the adult,” Annals of the Parakeratosis, an interface dermatitis with basal vacuoliza- Rheumatic Diseases, vol. 30, no. 2, pp. 121–133, 1971. tion, or some necrotic keratinocytes are examples of epi- [8] P. Ruscitti, F. Ursini, P. Cipriani et al., “Poor clinical response in rheumatoid arthritis is the main risk factor for diabetes dermal changes. Although lymphadenopathy is a typical development in the short-term: a 1-year, single-centre, lon- AOSD symptom, there are few studies on the histology of the gitudinal study,” PLoS One, vol.12, no. 7, Article ID e0181203, lymph nodes, which are mostly case reports. *e enlarged lymph nodes of this patient had reactive paracortical hy- [9] Y. Jamilloux, M. Gerfaud-Valentin, T. Henry, and P. Seve, perplasia with dermatopathic changes on histological ex- “Treatment of adult-onset still’s disease: a review,” 1era- amination [20]. Other histopathological features include peutics and Clinical Risk Management, vol. 11, pp. 33–43, paracortical and diffuse hyperplasia and paracortical, fol- licular, and diffuse hyperplasia. Proliferation of arteries and [10] Y. K. Jeon, J. H. Paik, S. S. Park et al., “Spectrum of lymph lymph nodes and immunoblastic proliferation may be node pathology in adult onset still’s disease; analysis of 12 present. *e pathologic differential diagnosis includes ma- patients with one follow up biopsy,” Journal of Clinical Pa- thology, vol. 57, no. 10, pp. 1052–1056, 2004. lignant lymphomas such as Hodgkin’s lymphoma and [11] H.-A. Kim, J. E. Kwon, H. Yim, C.-H. Suh, J.-Y. Jung, and angioimmunoblastic T-cell lymphoma (AITL). In AITL, the J. H. Han, “*e pathologic findings of skin, lymph node, liver, neoplastic T cells are medium to large in size. Large lym- and bone marrow in patients with adult-onset still disease,” phoid cells with an abundant transparent cytoplasm, and Medicine, vol. 94, no. 17, p. e787, 2015. Hodgkin’s cells were not seen in our case [12, 21]. [12] S. Castañeda, R. Blanco, and M. A. Gonzalez-Gay, “Adult- onset still’s disease: advances in the treatment,” Best Practice and Research Clinical Rheumatology, vol. 30, no. 2, pp. 222– 4. Conclusion 238, 2016. [13] A. Yasmeen, R. Bhatt, R. Elbahnasawy, A. Khan, G. Ali, and AOSD is a rare disease that requires a high clinical index of S. Matto, “Adult onset still’s disease,” A Case Report BJMP, suspicion, and diagnosis of AOSD is difficult as there is no vol. 11, no. 1, Article ID a1107, 2018. clinical or paraclinical ascertainment of diagnosis. We [14] D. Y. Chen, J. L. Lan, F. J. Lin, and T. Y. Hsieh, “Proin- emphasize the important role of skin biopsy and histopa- flammatory cytokine profiles in sera and pathological tissues thology in early diagnosis of this rare disease to achieve of patients with active untreated adult onset still’s disease,” complete relief of symptoms and save the patient from Journal of Rheumatology, vol. 31, no. 11, pp. 2189–2198, 2004. severe complications. [15] C. I. Joung, H. S. Lee, S. W. Lee et al., “Association between HLA-DR B1 and clinical features of adult onset still’s disease in Korea,” Clinical and Experimental Rheumatology, vol. 21, Data Availability no. 4, pp. 489–492, 2003. [16] A. Ohta, M. Yamaguchi, T. Tsunematsu et al., “Adult still’s Data are available and can be obtained on request to the disease: a multicenter survey of Japanese patients,” Journal of corresponding author. Rheumatology, vol. 17, no. 8, pp. 1058–1063, 1990. Case Reports in Immunology 5 [17] C. Perez, M. Montes, M. Gallego, and E. Loza, “Atypical presentation of adult still’s disease with generalized rash and hyperferritinaemia,” British Journal of Dermatology, vol. 145, no. 1, pp. 187-188, 2001. [18] J. Kelly, P. Chowienczyk, and T. Gibson, “Sore throat and hyperferritinaemia,” Journal of the Royal Society of Medicine, vol. 94, no. 8, pp. 400-401, 2001. [19] A. Cozzi, A. Papagrigoraki, D. Biasi, C. Colato, and G. Girolomoni, “Cutaneous manifestations of adult-onset still’s disease: a case report and review of literature,” Clinical Rheumatology, vol. 35, no. 5, pp. 1377–1382, 2016. [20] A. Z. Qureshi, M. AlSheef, W. T. Qureshi, and W Amjad, “Adult onset still’s disease with dermatopathic lymphade- nopathy,” Saudi Medical Journal, vol. 37, no. 11, pp. 1265–1267, 2016. [21] S. R. S. Njonnou, M. S. Soyfoo, and F.-A. Vandergheynst, “Efficacy of sarilumab in adult-onset still’s disease as a cor- ticosteroid-sparing agent,” Rheumatology, vol. 58, no. 10, pp. 1878-1879, 2019. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Immunology Hindawi Publishing Corporation

Adult-Onset Still’s Disease with Dermatopathic Lymphadenitis Clinicopathologic Features: A Rare Case Report and Review of the Literature

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Hindawi Case Reports in Immunology Volume 2022, Article ID 1653683, 5 pages https://doi.org/10.1155/2022/1653683 Case Report Adult-Onset Still’s Disease with Dermatopathic Lymphadenitis Clinicopathologic Features: A Rare Case Report and Review of the Literature 1,2 3 1,4 5 Reda A. Elhawary, Mir Nadeem , Mohammed S. Abdelwahed, Mansour Somaily, and Shahenda Y. Alemam Department of Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt Department of Pathology, Histopathology Consultant, Khamis Mushyte General Hospital, Khamis Mushait, Saudi Arabia Department of Medicine, King Khalid University and Associated Hospital, Abha, Saudi Arabia Department of Pathology, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia Department of Medicine, Rheumatology Division, King Khalid University Medical City, Abha, Saudi Arabia Department of Medicine, Rheumatology Division, Khamis Mushyte General Hospital, Khamis Mushait, Saudi Arabia Correspondence should be addressed to Mir Nadeem; mirnadeem44@gmail.com Received 10 February 2022; Accepted 18 May 2022; Published 3 June 2022 Academic Editor: Necil Ku¨t¨ukç¨uler Copyright © 2022 Reda A. Elhawary et al.  is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Adult-onset Still’s disease (AOSD) is an inŠammatory disorder characterized by fever, arthritis, and a transient skin rash. It is a rare condition characterized by inŠammatory multisystem changes of unknown cause. A 35-year-old woman was admitted to rheumatology department of tertiary care hospital complaining of painful wrist and skin rash as well as fever, generalized lymphadenopathy, weight loss, and fatigue.  e early diagnosis of AOSD was con“rmed by clinical history, examination, and laboratory tests, as well as a con“rmatory skin biopsy with typical histopathological features, namely, upper epidermal dys- keratosis and dermal inŠammatory neutrophilic in“ltration.  e patient’s condition was treated with steroids and NSAIDs, to which she responded well, and on follow-up, her symptoms regressed along with improvement in biochemical parameters.  e authors suggest that skin biopsy and con“rmation of histopathological diagnosis of AOSD are useful in the diagnosis and proper management of AOSD patients in cases with clinical suspicion of AOSD. untreated AOSD [3]. Still’s disease is named after the cli- 1. Introduction nician George Still, who “rst described it in children in 1896. Adult-onset Still’s disease (AOSD) is a rare inŠammatory In 1971, another clinician, Bywater, documented a similar disorder with a variety of clinical symptoms, including high- clinical presentation in 14 patients. Young adults are most grade fever, arthritis, a transient rash, lymphadenopathy, commonly a¢ected by the disease, which has a bimodal age distribution of 15–25 and 36–46 years [4]. Several classi“- and multiple organ involvement [1].  e annual incidence of AOSD has been estimated between 0.16 and 0.4 per 100,000 cation criteria have been proposed; however, the Yamaguchi people worldwide, with the reported prevalence rates from 1 criteria [5] are the most widely cited and provide the highest to 34 cases per 1 million people [2].  e incidence of AOSD sensitivity (93%) within these criteria, and the exclusion of remains low due to underdiagnosis of the condition and the other diseases is required. Fautrel et al. [6] proposed a new insidious nature of the disease. Macrophage activation set of criteria that added serum ferritin and glycosylated syndrome (MAS) and disseminated intravascular coagula- ferritin levels, but no exclusion criteria were included.  e tion (DIC) are two life-threatening consequences of sensitivity and speci“city of Fautrel criteria are 80.6% and 2 Case Reports in Immunology 98.5%, respectively. *e outcome of AOSD is unpredictable, performed, which revealed a preserved normal lymph node and the disease is conventionally divided into three different architecture, reactive lymphoid follicles, and marked para- cortical expansion with irregular pale areas (Figure 3) subtypes based on disease evolution: monophasic course, usually a single cyclic course, intermittent course, and, fi- consisting of numerous foamy histiocytes with brown nally, chronic course. *e condition in patients with melanin pigment, interdigitating dendritic cells, and monophasic course usually resolves within weeks to months Langerhans cells mixed with small lymphocytes. and regresses completely in less than a year [7]. Gluco- Eventually, the patient was diagnosed with adult-onset corticoids (GCs) commonly induce a dramatic clinical re- Still’s disease with associated dermatopathic lymphadenitis sponse, even within few hours and days; the higher dosages characterized as the monocyclic clinical pattern of AOSD. are reported as being more efficient than lower dosages *e patient was treated with anti-inflammatory drugs, a low leading to subsequent less relapses of the disease [8]. *e dose of the steroid methylprednisolone 1mg/kg for two reduction of concomitant glucocorticoids dosage following weeks, and nonsteroidal anti-inflammatory drugs (NSAIDs) treatment with the IL-1 receptor antagonist is seen in adult- were administered because of the active arthritis. *e patient improved after treatment, and upon two weekly follow-up onset Still’s disease [9]. Methotrexate and other disease- modifying antirheumatic drugs (DMARDs) are commonly for six months clinically, the patient had no fever, her ar- used to treat severe acute inflammatory synovitis [10]. In thritis improved, rash resolved, and ESR and C-reactive addition to DMARDs, biologic agents are used to treat protein (CRP) were negative. Clinically, there was no refractory AOSD, including TNF-α inhibitors (infliximab, lymphadenopathy with no further rheumatological etanercept) and IL-1 (anakinra, canakinumab) and IL-6 complaints. blockers (tocilizumab, sarilumab) [11]. 2.1. Ethical Declaration. *e case report was conducted in 2. Case Report full compliance with the Declaration of Helsinki and according to the research guidelines, and informed consent A 35-year-old woman presented to the rheumatology clinic was obtained from the patient for publication as a rare case of a tertiary care hospital in Aseer complaining of wrist report. Ethical approval from the institution was not needed pain and skin rash started 4 months ago. *e patient had for case report publication. accompanying symptoms such as weight loss, fatigue, in- ability to climb stairs, and inability to raise her arm above her head. *e patient had no significant past medical 3. Discussion history. On examination, the patient had polyarthritis with bilateral arthritis of the hand (metacarpophalangeal, in- George Still in 1896 recognized a clinical picture in children terphalangeal) and shoulder joints and a maculopapular that resembled polyarthritis in adults and named it Still’s erythematous rash affecting both extremities. After 2 days disease, which is the eponymous term for juvenile idiopathic of admission, the patient developed a fever which was high arthritis. In 1971, a number of adult patients were observed grade, and the maximum recorded temperature of 102.4 F to have features similar to children with juvenile arthritis occurred in the late afternoon. Laboratory investigations and did not meet the criteria for classic rheumatoid arthritis, revealed leukocytosis with TLC (16000/l), anemia (hae- so the term adult Still’s disease was coined to describe these moglobin 9 gm/dl), elevated ESR (50 mm/h) and C-reactive patients [6]. *e etiology of AOSD is unclear; however, protein (CRP 88mg/l), and serum ferritin (8000 ng/ml), genetic variables and various infectious triggers have been proposed as key etiologic features. However, confirmation of and CTscan of the thorax and abdomen and pelvis showed generalized lymphadenopathy without any significant in- an infectious etiology is still under investigation, and the fective focus with cervical lymphadenopathy largest one evidence for genetic components is inconclusive. *ere is measuring 2.3∗3.2 cm in left submandibular region also uncertainty regarding the presence of the same etiopatho- bulky bilateral axillary lymph nodes largest measuring genic factors among all the AOSD patients, and it has always 3.3∗2.3 cm along with mediastinal and para-aortic lymph been a cause of concern. Various pathogens, including vi- nodes. Rheumatoid factor (RF), anti-CCP, and antinuclear ruses and bacteria, have been studied to determine their antibody (ANA) tests were negative. *e differential di- involvement in the pathogenesis of AOSD. Bacterial path- agnoses in addition to AOSD, at the preliminary evalua- ogens include Yersinia enterocolitica and Mycoplasma tion, were mixed connective tissue disease, rheumatoid pneumonia [8]. Studies have been conducted on the im- arthritis, and psoriatic arthritis. munogenetics of AOSD, and a study on 62 French patients Punch biopsy of the skin was done in coordination with found an association between HLA-B17, -B18, -B35, and the dermatology department in day care, and it revealed -DR2 and AOSD. However, the study has not been validated epidermal dyskeratotic keratinocytes mainly in the upper by a larger investigation [9]. Fever, rash, sore throat, and layers of the epidermis and focally in the stratum corneum arthralgia are the common symptoms of AOSD [12]. Fever is (Figure 1). *ere was a superficial perivascular, periadnexal, usually above 39.0 C, and peak temperatures are observed in and interstitial inflammatory infiltrate rich in neutrophils the late afternoon and early evening [13]. *e normal rash in and few lymphocytes (Figure 2). *ese histologic features are AOSD is asymptomatic and defined as salmon-colored, consistent with Still’s disease in adults. To rule out the maculopapular eruptions affecting mainly the trunk and possibility of lymphoma, a lymph node biopsy was extremities. However, in active AOSD, an unusual, Case Reports in Immunology 3 Figure 1: Adult onset Still disease, skin biopsy with multiple individual dyskeratotic keratinocytes in the upper epidermal layers (thin arrows) and perivascular neutrophilic inflammatory infiltrate (thick arrow) (H&E X100). (a) (b) Figure 2: Adult onset Still disease, (A) skin biopsy with (a) multiple individual dyskeratotic keratinocytes in the upper epidermal layers (thin arrows) and (b) perivascular neutrophilic inflammatory infiltrate (thick arrow) (H&E X400). (a) (b) Figure 3: Dermatopathic lymphadenopathy. (a) Subcapsular nodular showing palely stained area in the paracortical region. Hyperplastic lymphoid follicles are also present (H&E X100). (b) Numerous pigment-containing histiocytes were present in the pale stained area (H&E X400). nonevanescent rash with pruritic, persistent papules or both important signs of AOSD and may be associated with plaques has been observed in addition to the conventional odynophagia [15]. Several cytokines, including tumor ne- rash [14]. Sore throat and an increase in serum ferritin are crosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-18, 4 Case Reports in Immunology have been associated with the pathophysiology of AOSD. Conflicts of Interest *e levels of these cytokines are extremely high in people *e authors declare that they have no conflicts of interest. with active AOSD [3]. *e knees, wrists, ankles, and elbows are affected. During febrile episodes, joint symptoms usually worsen [16]. References In our case, laboratory tests showed a high ESR (50) and leukocytosis (16000) with a preponderance of neutrophils. [1] K. S. Eardley, K. Raza, D. Adu, and R. D. Situnayake, “Gold treatment, nephrotic syndrome, and multi-organ failure in a AOSD is characterized by a disproportionately high serum patient with adult onset still’s disease,” Annals of the Rheu- ferritin level (6000). Hyperferritinemia affects approxi- matic Diseases, vol. 60, no. 1, pp. 4-5, 2001. mately 70% of patients and was previously considered to be [2] K. J. Evensen and H. C. Nossent, “Epidemiology and outcome due to cytokine production triggered by the reticuloendo- of adult-onset still’s disease in Northern Norway,” Scandi- thelial system or liver injury [17]. As in our diagnostic case navian Journal of Rheumatology, vol. 35, no. 1, pp. 48–51, report, rheumatoid factor and antinuclear antibodies were usually negative [18]. AOSD as a diagnosis of exclusion [3] R. Giacomelli, P. Ruscitti, and Y. Shoenfeld, “A compre- required a thorough examination including skin biopsy, hensive review on adult onset still’s disease,” Journal of Au- which was performed. Histopathologic examination of the toimmunity, vol. 93, pp. 24–36, 2018. rash in this case revealed dyskeratotic cells confined to the [4] M. Kurasawa, K. Kotani, G. Kurasawa, K. Shida, S. Yamada, and T. Tago, “Adult-onset still’s disease in a patient over 80 upper epidermis and stratum corneum, perivascular neu- years old successfully treated with low-dose methotrexate trophilic inflammatory infiltration of the upper dermis, and therapy,” Age and Ageing, vol. 36, no. 1, pp. 104–106, 2006. nuclear debris. *e specific histological features of the rash [5] M. Yamaguchi, A. Ohta, T. Tsunematsu et al., “Preliminary in AOSD patients have been documented in several pub- criteria for classification of adult still’s disease,” Journal of lications such as Cozzi et al. [19], with dyskeratosis confined Rheumatology, vol. 19, pp. 424–430, 1992. to the upper epidermis and stratum corneum serving as an [6] B. Fautrel, E. Zing, J.-L. Golmard et al., “Proposal for a new set important diagnostic marker, as explained by neutrophil and of classification criteria for adult-onset still disease,” Medicine, lymphohistiocytic infiltration of the upper dermis and vol. 81, no. 3, pp. 194–200, 2002. dermal mucin deposits are among the additional features. [7] E. G. Bywaters, “Still’s disease in the adult,” Annals of the Parakeratosis, an interface dermatitis with basal vacuoliza- Rheumatic Diseases, vol. 30, no. 2, pp. 121–133, 1971. tion, or some necrotic keratinocytes are examples of epi- [8] P. Ruscitti, F. Ursini, P. Cipriani et al., “Poor clinical response in rheumatoid arthritis is the main risk factor for diabetes dermal changes. 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Park et al., “Spectrum of lymph lymph nodes and immunoblastic proliferation may be node pathology in adult onset still’s disease; analysis of 12 present. *e pathologic differential diagnosis includes ma- patients with one follow up biopsy,” Journal of Clinical Pa- thology, vol. 57, no. 10, pp. 1052–1056, 2004. lignant lymphomas such as Hodgkin’s lymphoma and [11] H.-A. Kim, J. E. Kwon, H. Yim, C.-H. Suh, J.-Y. Jung, and angioimmunoblastic T-cell lymphoma (AITL). In AITL, the J. H. Han, “*e pathologic findings of skin, lymph node, liver, neoplastic T cells are medium to large in size. Large lym- and bone marrow in patients with adult-onset still disease,” phoid cells with an abundant transparent cytoplasm, and Medicine, vol. 94, no. 17, p. e787, 2015. Hodgkin’s cells were not seen in our case [12, 21]. [12] S. Castañeda, R. Blanco, and M. A. Gonzalez-Gay, “Adult- onset still’s disease: advances in the treatment,” Best Practice and Research Clinical Rheumatology, vol. 30, no. 2, pp. 222– 4. Conclusion 238, 2016. [13] A. Yasmeen, R. Bhatt, R. Elbahnasawy, A. Khan, G. Ali, and AOSD is a rare disease that requires a high clinical index of S. Matto, “Adult onset still’s disease,” A Case Report BJMP, suspicion, and diagnosis of AOSD is difficult as there is no vol. 11, no. 1, Article ID a1107, 2018. clinical or paraclinical ascertainment of diagnosis. We [14] D. Y. Chen, J. L. Lan, F. J. Lin, and T. Y. Hsieh, “Proin- emphasize the important role of skin biopsy and histopa- flammatory cytokine profiles in sera and pathological tissues thology in early diagnosis of this rare disease to achieve of patients with active untreated adult onset still’s disease,” complete relief of symptoms and save the patient from Journal of Rheumatology, vol. 31, no. 11, pp. 2189–2198, 2004. severe complications. [15] C. I. Joung, H. S. Lee, S. W. Lee et al., “Association between HLA-DR B1 and clinical features of adult onset still’s disease in Korea,” Clinical and Experimental Rheumatology, vol. 21, Data Availability no. 4, pp. 489–492, 2003. [16] A. Ohta, M. Yamaguchi, T. Tsunematsu et al., “Adult still’s Data are available and can be obtained on request to the disease: a multicenter survey of Japanese patients,” Journal of corresponding author. Rheumatology, vol. 17, no. 8, pp. 1058–1063, 1990. Case Reports in Immunology 5 [17] C. Perez, M. Montes, M. Gallego, and E. Loza, “Atypical presentation of adult still’s disease with generalized rash and hyperferritinaemia,” British Journal of Dermatology, vol. 145, no. 1, pp. 187-188, 2001. [18] J. Kelly, P. Chowienczyk, and T. Gibson, “Sore throat and hyperferritinaemia,” Journal of the Royal Society of Medicine, vol. 94, no. 8, pp. 400-401, 2001. [19] A. Cozzi, A. Papagrigoraki, D. Biasi, C. Colato, and G. Girolomoni, “Cutaneous manifestations of adult-onset still’s disease: a case report and review of literature,” Clinical Rheumatology, vol. 35, no. 5, pp. 1377–1382, 2016. [20] A. Z. Qureshi, M. AlSheef, W. T. Qureshi, and W Amjad, “Adult onset still’s disease with dermatopathic lymphade- nopathy,” Saudi Medical Journal, vol. 37, no. 11, pp. 1265–1267, 2016. [21] S. R. S. Njonnou, M. S. Soyfoo, and F.-A. Vandergheynst, “Efficacy of sarilumab in adult-onset still’s disease as a cor- ticosteroid-sparing agent,” Rheumatology, vol. 58, no. 10, pp. 1878-1879, 2019.

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Case Reports in ImmunologyHindawi Publishing Corporation

Published: Jun 3, 2022

References