Systemic juvenile idiopathic arthritis, with tinea capitis and peripheral eosinophilia: a case report

Abstract

Background:

Systemic juvenile idiopathic arthritis (SJIA) is a unique subtype of juvenile idiopathic arthritis (JIA) with very special clinical manifestations, complications, and management options. The simultaneous presentation of tinea capitis and eosinophilia has not been reported in the context of Systemic Juvenile Idiopathic Arthritis before.

Case presentation:

A 5-year-old Sudanese boy presented with fever and bilateral ankle arthritis in a background of extensive scalp lesions, which were scaly, itchy, and associated with hair loss. On examination: his weight was on the fifth percentile. There was cervical lymphadenopathy, hepatomegaly, and signs of bilateral ankle arthritis. Complete blood counts revealed leucocytosis, thrombocytosis, mild eosinophilia, and microcytic hypochromic anemia. Anti-dsDNA was positive with equivocal ANA profile, CRP was 34.4 mg/l, and LDH was very high. The patient received antibiotics, systemic antifungal, corticosteroids, hydroxychloroquine for which he achieved good results.

Discussion:

These results support the diagnosis of SJIA in a background of a tinea capitis with mild eosinophilia. Several case reports described extensive dermatophytosis in the background of other autoimmune diseases. The etiology of the eosinophilia was mysterious.

Conclusion:

Physicians should be alert to the presentation of systemic JIA. The association between SJIA, tinea capitis, and eosinophilia remained largely mysterious, and multicenter studies are needed to explore this further.

Background

Juvenile idiopathic arthritis is a group of arthritis that occurs before the age of 16 years. It lasts more than 6 weeks after the exclusion of other etiologies. It is classified according to the International League of Associations for Rheumatology (ILAR) into three subtypes according to the clinical manifestations, complications, and therapeutic options^[1–3]. Systemic-onset juvenile idiopathic arthritis (SJIA) is a very special subtype of juvenile idiopathic arthritis (JIA) that is characterized by fever which has a characteristic two spikes (>39°C) per day^[4]. About 80% of patients with this disease have a transient salmon-colored macular or maculopapular rash accompanying the fever. They may also have myalgia, tenosynovitis, and arthritis, which can be oligoarticular to polyarticular^[3]. The widely affected joints include wrists, knees, and ankles; but any joint can be affected, even the temporomandibular joints, cervical spine, hips, and the small joints of the hand and feet^[5–7]. SJIA may present with painless lymphadenopathy (25%) hepatomegaly, splenomegaly, or pericarditis which may be complicated by cardiac tamponade^[3,4]. Anemia, neutrophilic leucocytosis, thrombocytosis, high ESR, high CRP, high serum ferritin, low serum albumin, mildly elevated AST, high D-dimer, and negative autoantibodies are suggestive of the disease^[3].

HIGHLIGHTS

• Systemic juvenile idiopathic arthritis (SJIA) is a subtype of juvenile idiopathic arthritis with some extraarticular features such as lymphadenopathy, hepatospleenomegaly, rash and fever. Tinea capitis is a dermatophyte infection of the scalp, which is sometimes accompanied by a dermatophytid reaction.

• Several case reports described extensive dermatophyte infections in the setting of autoimmune diseases such as systemic lupus erythematosus, while others reported cases of eosinophilia in the setting of the dermatophyte infection that responded to medical treatment.

• This is a case report that documents the simultaneous occurrence of SJIA, extensive tinea capitis and eosinophilia.

• Studies are needed to explore why some patients may have extensive dermatophyte infections and to explain why eosinophilia may accompany the clinical picture.

The treatment of JIA focuses on suppressing inflammation, preserving functions, and preventing deformity and blindness^[8,9]. The currently available drugs include nonsteroidal anti-inflammatory drugs (NSAID), Systemic corticosteroids, and Disease-modifying anti-rheumatic drugs (DMARDs)^[3,10,11].

Tinea capitis is the most common dermatophyte infection, which affects the scalp and associated hair follicles^[12]. In Port Sudan, eastern Sudan, it affects 17% of school-aged children^[13]. The transmission may occur from human, animal, or soil to the patient. The interplay between the fungi virulence and the host immunity affects the clinical manifestation of the disease^[12]. A dermatophytid reaction is an immunological reaction to the antigens of dermatophytes, which may occur before or after antifungal treatment^[14]. Its prevalence in an old study in Jerusalem was 0.2%, but a recent study in Turkey suggested a higher prevalence^[14,15]. The manifestations of id reaction may range from asymptomatic isolated eosinophilia, cutaneous eruptions, to severe systemic manifestations such as fever, anorexia, generalized lymphadenopathy, splenomegaly, arthritis, or even anaphylaxis^[14,16,17].

Eosinophilia in developing countries appears in the context of parasitic infections and allergic conditions^[18]. Eosinophils release their granules in response to fungal antigens, which mediate allergic bronchopulmonary mycosis^[19]. Moreover, a case report of kerion-associated eosinophilia was described, in which a dermatophytid reaction was thought to be the cause, which responded well to corticosteroids and antifungal therapy^[17]. Two case reports of two patients with systemic lupus erythematosus in which tinea capitis was disseminated, one of them was using steroids while the other was not^[20,21].

This is the first case that is trying to understand the interplay between juvenile idiopathic arthritis, eosinophilia, and tinea capitis. Reporting of this case was compliant with TITAN and SCARE guideline checklists^[22,23]. No AI was used in the research and manuscript development.

Case presentation

History

A 5-year-old Sudanese male from Algazira state, central Sudan presented with bilateral ankle swelling, bilateral knee and hip pain, and fever, which started 1 month prior to presentation. His mother was also concerned about scales all over his scalp that are associated with itching, and hair loss, which started 2 months prior to presentation. His symptoms started insidiously with the fever mainly at night and relieved with antipyretics. He had anorexia and weight loss but neither abdominal pain, vomiting, diarrhea, cough, upper respiratory tract symptoms, headache nor history of trauma. He had a history of right knee swelling which was resolved spontaneously. Otherwise, past history was unremarkable. He had no family history of atopy, autoimmune disease, or malignancy and was not on any medications. Vaccinations were up to date according to the guidelines of the Sudanese Ministry of Health.

Examination

On examination, the patient was ill but not pale, jaundiced, or cyanosed. His weight was 15 kg (along the 5th centile). The scalp had white-yellow scales with some swelling, hair loss, and dried pus all over the scalp, but more on the vertex and both temples (see Fig. 1). The scalp has redness and is tender to palpation. There was bilateral cervical lymphadenopathy, which was mildly tender, and discrete, and a maximum diameter was 1 × 1 cm.

Figure 1.

A 5-year-old child with a patch of hair loss; representing tinea capitis involving the vertex and both temples.

Both ankle joints were swollen and tender to palpation, and movement was restricted (refer to Fig. 2). Other joint examinations were normal. Abdominal examination was soft, with palpable liver, which was 4 cm below the costal margin, and palpable para-aortic lymph nodes, but no splenomegaly was detected by examination. Bowel sounds were normal. Chest and cardiovascular examination was normal.

Figure 2.

A 5-year-old child with bilateral swollen ankles.

Investigations

The patient had mild neutrophilic leucocytosis, mild eosinophilia, and microcytic anemia with thrombocytosis. Urinalysis was normal. Anti-dsDNA antibody was positive, but ANA was equivocal (refer to Table 1).

Table 1.

Laboratory investigation for the case

Test	Finding
WBC count differential	13.4 × 103 cell/mm3
Neutrophil percentage	49%
Lymphocyte percentage	38%
Eosinophil percentage	8%
Platelet count	614 × 103 cell/mm3
Hemoglobin	10.3 g/dL
MCV	71.8 fL
MCH	22.3 pg
MCHC	31.1 g/dL
Urinalysis	Normal
Stool for ova and parasite	Negative
Anti-dsDNA antibody	45 IU/mL (positive)
ANA profile	0.8 Ratio (equivocal)
CRP	34.4 mg/L (high)
ESR	49 mm/h
LDH	Very high

WBC = white blood cell, MCV = mean corpuscular volume, MCH = mean corpuscular hemoglobin, MCHC = mean corpuscular hemoglobin concentration, anti-dsDNA = anti-double-stranded DNA, ANA = anti-nuclear antibody, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, LDH = lactate dehydrogenase

The patient received Methylprednisolone, Hydroxychloroquine, griseofulvin, antibiotics and supplements of calcium, and vitamin D (refer to Table 2).

Table 2.

Drug regimen details of some medications, which were prescribed to the patient

Dose	Regimen
Methylprednisolone	30 mg/kg/day for 3 days, followed by oral prednisone 1 mg/kg/day
Hydroxychloroquine tabs	5 mg/kg/day
Griseofulvin syrup	7.3 mg/kg/day

After 1 month of treatment, the patient condition improved and was referred to the ophthalmologist for a slit lamp examination.

Discussion

In this case, ANA was not positive, which is the case in 94–96% of cases of SJIA^[3,21] Anti-dsDNA was most likely false positive, that is why it is not recommended to test it with negative ANA, as this excludes SLE^[24]. While the elevated LDH may be alarming to macrophage activation syndrome (MAS), which is a severe complication of SJIA due to cytokine storm, which presents as resistant pyrexia and systemic inflammation, but fortunately, in our case the fever was not with this pattern^[25]. Normal serum ferritin and the ESR, which did not rise during the admission course, were also against MAS^[26,27].

Another important differential diagnosis was malignancy, which was excluded by the peripheral blood picture and the resolution of symptoms and signs with the treatment. So the full detailed history, proper clinical examination and laboratory findings are in favor of the diagnosis of systemic juvenile idiopathic arthritis.

Mild peripheral eosinophilia explanation in our case was challenging; whether it is related to a dermatophytid reaction with no obvious morbilliform or lichenoid lesions, or due to other causes. Drug-induced tubulointerstitial nephritis was excluded from the laboratory and history findings. Occult helminthic infection is also unlikely because the patient has no supporting gastrointestinal symptoms or signs and negative stool microscopy. Another logical explanation is an undiagnosed allergic disease in a background of tinea capitis, which is prevalent in public schools according to a study in Port Sudan^[28]. Occult dermatophytid reaction may be an explanation, which is consistent with the same observation from another case report of kerion due to T. tonsurans with 21% eosinophil in the complete blood count, which was reduced to 6% 1 month later after oral griseofulvin and corticosteroid use^[17]. However, unlike that case in which the patient was a 45-year-old female with a clear medical background, unlike our patient. Eosinophils recognize β-glucan of the fungal cell wall and react to it by releasing its granules in allergic brochopulmonary aspergellosis^[29]

A 26-year retrospective cohort study reported 39% eosinophilia prevalence among SJIA patients, some of them even before initiation of the biological treatment. The explanation of eosinophilia in those patients was also a matter of discussion; whether due to a side effect of medication (DRESS), or simply unknown. Those cases with eosinophilia were more likely to develop Macrophage Activation Syndrome (MAS), and drug reactions. In that cohort, treatment resolved eosinophilia in some cases, which is similar to our case report^[30,31].

Does tinea capitis occur more extensively in this patient due to the disease itself? We don’t know fully, but in a previous case report to a patient with systemic lupus erythematosus with disseminated infection at the time of the diagnosis before even the use of corticosteroid^[20]. In that case, the causative agent was Microsporum gypseum but unfortunately in our case, the diagnosis was made clinically only, and microbiological consultation was not ordered due to financial problems.

The patient suffered from scalp itching, hair loss, and examination revealed broken hair shafts with a background of erythema, swelling, and corresponding lymphadenopathy. This constellation of symptoms and signs resolved with the antifungal treatment, which makes the diagnosis most likely tinea capitis.

In this case, there is occurrence of tinea capitis in a background of SJIA with eosinophilia. What makes our case unique is its association with systemic juvenile idiopathic arthritis and not Systemic lupus erythematosus even before the start of immunosuppressive therapy^[20,21]. We recommend further multicentered studies about the immune response against fungi in the setting of juvenile idiopathic arthritis with more focus on the SJIA. We recommend further studies on the eosinophils and their role in tinea capitis and autoimmune diseases, especially systemic juvenile idiopathic arthritis.

Conclusion

Physicians should be alert to the presentation of systemic JIA. Careful follow-up of prolonged febrile patients with arthritis of unknown origin is important to reach the diagnosis. Further studies are needed to assess the immune response in the SJIA setting. The association between SJIA, tinea capitis, and eosinophilia remained largely mysterious, and multicentered studies are needed to explore this more.

Ethical approval

Not applicable, as the study is a case report in which no identifying information of the patient was published.

Consent

The authors confirm that informed verbal consent was obtained from the parents for this article’s publication and to display of the images. No identifiable information has been written.

Source of funding

The authors declare that no external funding was used to report or publish this study.

Author contributions

A.B.M.A. contributed greatly to the article, from data documentation and direct supervision of the case during admission and follow-up. M.G.A.I. and A.B.M.E. wrote the introduction and discussion sections and ensured compliance with the guidelines. M.E. supervised the team. All authors read and approved the final manuscript.

Conflicts of interest disclosure

The authors declare that there is no conflict of interest to disclose.

Research registration unique identifying number (UIN)

Not applicable.

Guarantor

Albraa Babiker Mohammed Alameen.

Peer and provenance

Not commissioned, externally peer-reviewed.

Data availability statement

Data is publicly available.