A case of likely acute febrile neutrophilic dermatosis in a 17-year-old male presenting to general paediatrics
- 1 Lewisham and Greenwich NHS Foundation Trust, London, UK
- 2 Children's Services, Medway NHS Foundation Trust, Gillingham, Kent, UK
- Correspondence to Dr Arameh Aghababaie; a.aghababaie@nhs.net
Abstract
We present the case of a 17-year-old male with a sore throat, tender cervical lymphadenopathy, bilateral erythematous and enlarged tonsils, fever, joint pain, widespread tender purpuric nodules, ulcerative lesions and erythematous pustules. The diagnosis was initially unclear. He had raised neutrophils, erythrocyte sedimentation rate and C-reactive protein. His skin biopsy showed a neutrophilic dermatosis with superficial pustulosis and leukocytoclastic vasculitis. Most likely, the patient suffered from a rare condition called acute febrile neutrophilic dermatosis (AFND). AFND is a very rare disorder of poorly understood aetiology, with only a few hundred reported cases in the literature. The complexity and rarity of this condition, and the difficulty in diagnosing, is an example of the challenge facing paediatricians as the paediatric admission age threshold increases to include older adolescents and young adults up to the age of 25 years, as per the National Health Service (NHS) long-term plan.
Background
Acute paediatrics continues to be a general and broad specialty within UK practice, diagnosing conditions of children and adolescents within the context of their physical, developmental and mental health. Traditionally, paediatric departments have accepted patients from the age of 0 to 16 years. However, a growing number of hospitals are increasing the paediatric admission age threshold to 18 years (consistent with the legal definition of adulthood in the UK), and the National Health Service (NHS) long-term plan advocates continuity of care from birth to 25 years of age as a priority over the next decade.1
These imperatives pose challenges for paediatricians, increasingly faced with young adults who may present with complex and perhaps unfamiliar symptoms and signs. Young adults may also have more risk factors to which younger children are less likely to be exposed (eg sex, alcohol, smoking, drug abuse, and occupational hazards).
Therefore, we present a case that aims to highlight these diagnostic challenges among young adults and to emphasise the need for paediatricians to familiarise themselves with conditions that are more often encountered in adult medicine. This will be even more crucial for paediatricians once the paediatric admission age threshold increases to 25 years of age, as per the NHS long-term plan.1
In this case report, we discuss the presentation and management of a 17-year-old male with fevers, cervical lymphadenopathy, joint pains and unfamiliar skin lesions.
Case presentation
A 17-year-old white-British male presented to the paediatric assessment unit at a District General Hospital with an acute limp. He also reported a ‘lump in the neck’ and sudden-onset rash. On further questioning, he had been experiencing bilateral elbow, hip and knee joint pain for 7 days. The ‘neck lump’ only became noticeably large in the recent 5 days. In the previous 2 days, he had an outbreak of a painful, stinging, non-pruritic rash on his arms, legs, back and scalp. Prior to the onset of these symptoms, he had a sore throat with mild haemoptysis, with fever and mild fatigue. He denied any recent weight loss, night sweating, rigours, nausea, vomiting, abdominal cramping, dysuria or altered bowel habit.
He was previously well, on no regular medications, nor was he known to have allergies. He received all necessary vaccinations during his childhood. His family history includes non-Hodgkin’s lymphoma (paternal grandmother) and psoriasis (maternal grandmother). He lives with his mother at home and works as a plumber. He is sexually active and claims to use protection while having intercourse. He also smokes cigarettes and marijuana socially. He had not travelled overseas recently.
His observations were as follows: the respiratory rate was 16 breaths/min, oxygen saturations were 97% on room air, heart rate was 91 beats/min, blood pressure was 119/74 mm Hg, the temperature was 38.3°C and his Glasgow Coma Scale score was 15/15.
On inspection, he had noticeable pallor and a bilaterally antalgic gait. On examination, his chest was clear and heart sounds were normal with no murmurs. There was no evidence of organomegaly. His tonsils were enlarged and mildly erythematous bilaterally, with no tonsillar exudates. He had profound bilateral non-tender cervical lymphadenopathy measuring 5×6×3 cm on both sides. No other lymph nodes were palpable. He had numerous purpuric nodules and ulcerative lesions and erythematous pustules (figure 1). The diameter of these lesions ranged from 0.5 cm to 5 cm. The lesions were found on his scalp, acral surfaces, back and the extensor surfaces of the arms and legs. The lesions were tender on palpation.
(A, C) Examples of the ulcerative and pustular lesions found on the patient’s ankle and hand. (B, D) Examples of the purpuric nodular lesions found on the patient’s ankle and leg.
The aetiology of his presentation was initially unclear. However, the most important differential to rule out was a paraneoplastic dermatoses secondary to lymphoma. We also considered psoriatic arthropathy, Stevens-Johnson syndrome, Systemic lupus erythematosus, sarcoidosis, Henoch-Schönlein purpura and infectious diseases such as HIV.
Investigations
The baseline blood investigation results were as follows: haemoglobin 141 g/L (130–170 g/L), white cell count 21.6×109/L (4–11×109/L) (neutrophils 17.4×109/L (2.0–8.0×109/L), lymphocytes 2.1×109/L (1.0–4.0×109/L), monocytes 1.7×109/L (0.1–1.0×109/L), eosinophils 0.4×109/L (0.0–0.4×109/L), basophils 0×109/L (0–0.3×109/L)), C-reactive protein (CRP) 199.4 mg/L (0–5 mg/L), sodium 139 mmol/L (133–146 mmol/L), potassium 4.4 mmol/L (3.5–5.3 mmol/L), urea 6.3 mmol/L (2.5–7.8 mmol/L), creatinine 60 µmol/L (59–104 µmol/L), albumin 35 g/L (35–50 g/L), alkaline phosphatase 164 U/L (30–130 U/L), alanine transferase 58 U/L (<50 U/L), bilirubin 10 µmol/L (0.0–21.0 µmol/L), adjusted calcium 2.31 mmol/L (2.2–2.6 mmol/L), phosphate 0.96 mmol/L (0.8–1.5 mmol/L), international normalised ratio 1.3 (0.8–1.2), prothrombin time 14.8 s (9.4–12.5 s), activated partial thromboplastin time 32 s (25.1–36.5 s), fibrinogen >7.1 g/L (2.8–4.7 g/L). The blood culture was negative. Urinalysis and urine culture were both negative. The blood film showed neutrophil leucocytosis with some toxic granulation, a left shift of neutrophils with many band forms, and occasional metamyelocytes.
In light of these results, an infective screen was performed. HIV, hepatitis B, hepatitis C, leptospirosis and gonorrhoea were all negative. Monospot and anti-streptolysin O titres were both negative and Epstein-Barr virus (EBV) IgM was not detected. However, EBV IgG was detected although he had not previously been diagnosed with glandular fever.
We performed further blood tests for oncological markers: creatine kinase 62 U/L (55–370 U/L), lactate dehydrogenase 429 IU/L (200–450 IU/L) and ferritin 225 ng/mL (24.0–337.0 ng/mL). We also performed blood tests for various rheumatological markers: erythrocyte sedimentation rate (ESR) was raised at 37 mm/hour (0–10 mm/hour), antinuclear antibody was negative, perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, myeloperoxidase was negative, and proteinase-3 was negative. We also performed thyroid function tests for completion which were normal (free T4 16.4 pmol/L (7.7–20.6 pmol/L); thyroid-stimulating hormone 3.14 mIU/L (0.3–4.8 mIU/L)).
We also performed radiological investigations. He had a chest X-ray which was normal. He also had an ultrasound of his neck which showed enlarged lymph nodes (the largest measuring 51×23 mm in the right submandibular gland region and 28×18 mm in the left submandibular gland region). The alteration in the echo-texture with a few small nodules within, and the distortion of vasculature suggested that the lymph nodes were unlikely to be reactive. The thyroid and submandibular glands were otherwise normal. He then had a CT of his neck, thorax, chest, abdomen and pelvis, which showed no obvious masses; however, there were appearances of hepatomegaly and generalised lymphadenopathy, raising the suspicion of a lymphoproliferative disease.
We then performed a fine-needle aspiration of the right submandibular lymph node which was sent for culture and histology. The culture was negative, and the histology showed appearances of an active acute lymphadenitis supporting a diagnosis of a benign reactive lymphadenopathy, with no diagnostic evidence of a lymphoma.
Skin biopsies were taken of his lesions which were cultured and grew no infective organisms. The histology of these skin biopsies showed evidence of neutrophilic dermatosis, superficial pyoderma, and superficial pustulosis, with leukocytoclastic vasculitis at the margins. There was no evidence of malignancy.
Treatment
Naproxen 500 mg three times per day orally was initially started to reduce inflammation and pain. Eventually, once the possibility of a malignancy was ruled out, a trial of prednisolone 30 mg once a day orally was commenced. The prednisolone dose was tapered and eventually stopped after a total 1 month course.
Outcome and follow-up
There was a dramatic improvement in joint inflammation and pain, and his lesions began to regress within 2 days following the beginning of steroid treatment. He was then discharged.
He was reviewed in the paediatric assessment unit 1 week later. He still had a mild limp; however, systematically he felt well in himself and the lesions were healing well. He was then reviewed in a dermatology clinic 2 weeks following discharge, and he was continued on prednisolone for a total 1 month course due to the positive response the steroids had on his clinical condition. The patient is currently alive and well. He returned to his job and normal day-to-day life very swiftly. He was seen in the paediatric assessment unit once again, 6 months following discharge, and there were no lesions on his body, and he did not report any persisting or recurring symptoms.
Discussion
The blood film, CT scan, lymph node and skin histology results, together with the raised inflammatory markers, raised ESR, and the detection of p-ANCA suggested an auto-inflammatory process. We correlated these results with his clinical symptoms and signs and considered various differentials such as periodic fever syndromes and acute febrile neutrophilic dermatosis (AFND) (also known as Sweet’s syndrome). The nature of his symptoms was not episodic nor was there any family history of this condition, making the former less likely. Additionally, AFND most commonly presents in the 30–50 year old age group, especially females.
There are diagnostic criteria for AFND, as proposed by von den Driesch2 (table 1). According to the criteria, the patient did indeed have an abrupt onset of tender and erythematous pustules, plaques, nodules, blisters and ulcers and the histology of these lesions showed a dense neutrophilic dermatosis. Although the criteria states that the skin histology should not show signs of leucocytoclastic vasculitis to qualify for an AFND diagnosis, there have been cases of severe AFND with evidence of vasculitis.3 4 p-ANCA is also a marker of vasculitis and was positive in this patient. There have been some reports of p-ANCA positivity in AFND.5 6
Diagnostic criteria for acute febrile neutrophilic dermatosis
| Major criteria | Minor criteria |
| Abrupt onset of tender or painful erythematous plaques or nodules, occasionally with vesicles, pustules or blisters | Fever >38°C |
| Histological evidence of dense neutrophilic dermal infiltrate without leucocytoclastic vasculitis | Abnormal laboratory values at presentation (3 of 4):
|
| Association with an underlying haematological or visceral malignancy, inflammatory disease or pregnancy, or preceded by an upper respiratory or gastrointestinal infection or vaccination | |
| Excellent response to treatment with systemic corticosteroids or potassium iodide. |
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This table has been adapted from von den Driesch and classifies the diagnostic criteria for AFND.2 To be diagnosed with AFND, patients should have two of the major criteria, and at least two of the minor criteria.2 Our patient fulfilled all criteria.
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CRP, C-reactive protein; ESR, erythrocyte sedimentation rate.
The patient also had an ESR of 37 mm/hour, a CRP of 199.4 mg/L, and leucocytes of 21.6×109/L, of which 17.3×109/L were neutrophils (80.1%), which fulfils another criterion for AFND (table 1).2
Symptomatically, he experienced fevers which fulfils another criterion (table 1).2 He also had arthritis which has been frequently reported in this condition, and he also had severe lymphadenitis; however, there is minimal established evidence to support the link between this and AFND.7
In retrospect, the autoimmune reaction was preceded by a sore throat, fever, mild haemoptysis and general malaise and fatigue. According to the associated triggers stated in the diagnostic criteria, we had ruled out malignancy, and therefore the most likely trigger was an upper respiratory tract infection (table 1).2 The only positive viral serology was EBV IgG, although EBV IgM was negative, meaning there was a past infection.8 However, his upper respiratory symptoms, with mild derangement of his liver function tests and clotting screen, and hepatomegaly and ‘lymphoproliferative disease’ (as per the CT scan and blood film) suggest a recent EBV trigger for this symptom cascade.9–11 AFND may also be idiopathic.
Lastly, the consensus first-line management of AFND is a course of steroids, and a good response suggests further support for the diagnosis (table 1).2 This further corroborates our suspected diagnosis, because our patient, as previously mentioned, exhibited a very rapid and effective response to prednisolone treatment.
Although there are a few atypical features, the patient fulfilled all diagnostic criteria for AFND. He presented with the classical skin lesions, fevers and arthralgia, which had profoundly improved following the administration of steroid treatment. This was highly likely to be triggered by an upper respiratory tract infection, such as EBV. AFND is a rare condition, with only a few hundred cases reported.3 Therefore, it is difficult to say whether the atypical features seen in this case are truly atypical. However, what we do know is that the patient presented with the cardinal signs of AFND; therefore, we can consider this case to be a likely atypical case of AFND.
Learning points
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Acute febrile neutrophilic dermatosis (AFND) must be considered in the differential diagnosis for young adults presenting with fever and tender skin nodules.
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Cervical adenopathy and arthritis, although uncommon, can be seen with AFND.3 Histological evidence of vasculitis and perinuclear antineutrophil cytoplasmic antibody positivity is also rare in AFND.4–7
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A short course of oral glucocorticoids produces a dramatic improvement in clinical symptoms of AFND.
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AFND is an example of a challenging presentation that paediatricians may encounter more frequently in practice, as the paediatric admission age threshold increases, as part of the National Health Service long-term plan.1
Acknowledgments
We would like to thank Dr Sarah Mehrtens from East Kent Hospitals NHS Foundation Trust and Dr Matthew Szeto from Medway NHS Foundation Trust for their respective adult dermatological and rheumatological opinions during the patient’s admission, which helped facilitate a deeper understanding of this case. We would also like to thank Professor John Schofield from Maidstone and Tunbridge Wells NHS Foundation Trust for providing images of the skin and lymph node histology slides to BMJ Case Reports for review. We would also like to express our gratitude to Dr Ann Fleming from Maidstone and Tunbridge Wells NHS Foundation Trust who provided insight and expertise that greatly assisted the research, although they may not agree with all of the conclusions of this paper.
Footnotes
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Contributors AA was involved in the clinical care of the patient, the diagnostic process, the clinical management of the patient, the conception of the case report, data collection and analysis and writing the first draft. RP was involved in the clinical care of the patient, the diagnostic process, the clinical management of the patient, proof-reading and editing the manuscript and supervision.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.
References
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