Diagnosis of Sweet’s syndrome in otolaryngology

Abstract

Sweet’s syndrome (acute febrile neutrophilic dermatosis) consists of acute onset of painful cutaneous erythematous lesions, mostly found in the upper extremities followed by the head and neck region, particularly in patients with underlying malignancies. We describe the case of a woman in her mid-30s, who was treated for acute myeloid leukaemia and presented with a severe painful and progressive erythematous lesion of the retroauricular skin. Clinical features, laboratory tests, blood cultures and histological biopsy yielded a diagnosis of Sweet’s syndrome. The treatment consisted of oral and topical corticosteroids and her signs and symptoms resolved within 1 week. Although Sweet’s syndrome is uncommon, awareness among otolaryngologists is crucial to ensure a prompt diagnosis, cure and referral to an oncologist (if not already involved) for patients with Sweet’s syndrome in the head and neck area.

Background

Sweet’s syndrome (acute febrile neutrophilic dermatosis) is a dermatological disorder of unknown aetiology, with acute onset of painful cutaneous erythematous lesions, mostly found in the upper extremities followed by the head and neck region. Due to toxic presentation of the patient, it might be confused with a septic infection leading to unnecessary treatment with antibiotics and delayed prednisone administration, which is the proper treatment. Sweet’s syndrome has been associated with autoimmune processes, malignancies, gastrointestinal and respiratory infections, drug reactions and inflammatory bowel disease. Several authors have suggested that the mechanism of action involves a dysregulation of immune function or an immunomediated hypersensitivity.^1–3

Both major and two out of four minor criteria should be met to diagnose Sweet’s syndrome, for which biopsy is crucial (table 1).^{4 5}

Table 1.

Diagnostic criteria of sweet’s syndrome^{4 5}

Major criteria	Minor criteria
Acute onset of painful erythematous lesions, respectively, nodules or plaques.	Fever (>38°C) and general malaise.
Infiltration of neutrophils into the dermis, without leucocytoclastic vasculitis.	Association with: Underlying malignancy. Pregnancy. Respiratory, gastrointestinal or vaccination-induced infection.
	At least three of four laboratory findings: Elevated C-reactive protein. Erythrocyte sedimentation rate >20 mm/hour. >70% neutrophils. Elevated leucocytes (>8000).
	Response to treatment with systemic corticosteroids.

*This table was published in von den Driesch⁵ and adjustments were made, with permission, using the criteria published in Su and Liu⁴.

Diagnosis depends on the clinical presentation and is based on exclusion of suspected infectious diseases by blood cultures and imaging.^{3 6} Histopathology shows an extensive interstitial neutrophil infiltrate in the upper dermis but varieties have been found, with neutrophil invasion in the epidermis or subcutis and presence of eosinophils and lymphocytes.³ Its association with paraneoplastic disease warrants the need for otolaryngologists to be aware of the condition to provide accurate treatment.^7–9 In this case report, we describe a rare case of Sweet’s syndrome with a particular presentation in the head and neck area.

Case presentation

A pregnant patient (G3P0, 30 weeks) in her mid-30s was admitted to the hospital’s haematology department due to acute myeloid leukaemia (AML) de novo for which she was given induction therapy. The otolaryngologist was consulted because of a progressive erythematous lesion of the retroauricular skin and the auricula of the left ear suspected for mastoiditis (figure 1). Both the auricle and retroauricular area were extremely painful when palpating. The patient did not report any problems regarding hearing loss, vertigo and other otological symptoms, apart from a retroauricular pustule 2 days before presentation. The patient had no significant history of ear, nose and throat disorders, except for a tonsillectomy in childhood. On physical examination, her vital signs showed a temperature of 39.6°C (103.3°F) since 2 days, a heart rate of 95 beats per minute and no further abnormalities. The left ear was protruding, mildly bulging and the retroauricular area was erythematous. Besides from a pre-existing preauricular sinus, no abnormalities of the right ear were found. The physical examination was notable for a normal otological examination, including normal pneumatic otoscopy. Both Rinne and Weber tuning fork tests were normal: Weber did not lateralise and Rinne was positive on both sides. Nasopharyngolaryngoscopy and oral examination did not reveal any abnormalities. There were no signs of meningitis and no fluctuation, crepitation or abnormalities in the neck region.

Figure 1.

Clinical pictures at presentation. Notice the distinctive swelling and redness of the retroauricular skin and the auricula of the left ear.

Investigations

Laboratory findings showed a pancytopenia, with a haemoglobin level of 70.90 g/L (normal: 119.20–154.60) and leucocytes, neutrophils and thrombocytes of 0.4×10⁹/L, 0.24×10⁹/L, 7×10⁹/L, respectively (normal: 4.0–10.0, 1.6–8.3 and 150–450, respectively). C reactive protein (CRP) was increased to 138 mg/L (normal: 0–10) versus 14 mg/L the day before for which she was treated by the haematologist with imipenem/cilastatin four times per day 500 mg and anidulafungin one time per day 100 mg over 24 hours. Routine blood cultures had not revealed any causatives of the possible infection yet. Following the diagnosis of erysipelas or cellulitis, provoked by a furuncle in an immune-compromised patient receiving imipenem/cilastatin, we decided to start analgesics and continue imipenem/cilastatin and anidulafungin, check every 2 hours the progressiveness of erythematous lesion by marking the affected area and wait for the blood culture results. However, the lesion expanded towards the preauricular area and level II of the neck (figures 2 and 3). The retroauricular skin remained status quo. The new working clinical differential diagnosis included skin disorders like erysipelas, cellulitis, erythema multiforme, pyoderma gangrenosum, a parotitis with or without abscess, a mastoiditis with abscess, lymphadenopathy with or without abscess and a superficial or deep abscess (based on bacterial, mycobacterial and deep fungal infections).

Figure 2.

Clinical picture 24 hours after starting antibiotics. Notice the expansion of the lesion towards the auricula.

Figure 3.

Clinical picture 24 hours after starting antibiotics. Notice the expansion of the lesion towards the parotid region.

The radiologist performed an ultrasound, which showed a diffuse abnormal hyperaemic area within and around the earlobe and the parotid gland. Furthermore, some reactive lymph nodes were seen, but there were no signs of a superficial abscess. Cytology of the earlobe showed no signs of bacterial infection or presence of invasive mycosis. Due to the impressive presentation of rapidly progressive septic condition, imaging possibilities were discussed. CT of the thorax had already been established by the haematologist and excluded a pulmonary focus. We did not perform further imaging, because we considered that the disadvantages outweighed the advantages of radiation exposure during pregnancy in this case for CT scan. Both modalities, such as CT or MRI of the neck, had no added value, because ultrasound did not reveal any superficial abscesses, making deep abscesses unlikely.¹⁰ Furthermore, a tissue sample was collected for histological examination and this reported an extensive interstitial neutrophil infiltrate, which suggested a reactive neutrophil dermatosis like Sweet’s syndrome and was unlikely to be caused by drugs (figures 4 and 5). Other possible diagnoses showing similar neutrophilic cell infiltrates are, for example, urticaria or a bacterial infection like erysipelas.^{11 12}

Figure 4.

Histopathology of biopsy of the skin (H&E 100×). ○ Subepidermal oedema, □ cell-rich dermis with interstitial neutrophils.

Figure 5.

Histopathology of biopsy of the skin (H&E 10×40).

Treatment

Consulting the dermatologist resulted in starting two times per day application of topical clobetasol corticosteroids type IV (Dermovate) until absence of induration appeared and prescription of a high dose weight-based oral prednisolone (1 mg/kg) for 1 week. We started with 80 mg prednisone one time per day for 2 days, followed by 40 mg for 2 days, 20 mg for 2 days and 10 mg for 1 day.

Outcome and follow-up

In total, the patient received prednisone for 1 week, while monitoring closely for relief of symptoms to avoid unnecessary prolonged use of prednisone during pregnancy. Cutaneous lesions resolved in 2 days accompanied by disappearance of symptoms. CRP decreased to 6 mg/L after 12 days. Unfortunately, recurrence occurred at the gynaecological labia, which was treated with topical clobetasol and 6 months later on the head and her back simultaneously with recurrence of AML, which was treated with oral prednisone. Shortly after this, the patient died of recurrence of AML 6 months after initial diagnosis.

Discussion

This case presents a pregnant patient, diagnosed with AML, with an extremely painful lesion of the ear accompanied by pancytopenia and fever with negative blood cultures. Diagnostic imaging and histological biopsy showed an extensive interstitial infiltrate, which suggests Sweet’s syndrome. Symptoms start with an acute onset of painful erythematous and often oedematous cutaneous lesions, accompanied by fever and elevation of neutrophils. Furthermore, patients might report of headaches, arthralgia and malaise.^{3 6 13} Single or multiple lesions can be found, with a preference of the upper extremities and head and neck region.^{6 14} Mucosal occurrence of the disease has been reported, with oral mucosa being mostly affected in patients with underlying malignancy.^{15 16}

Sweet’s syndrome is an acute febrile neutrophilic dermatosis and has been described for the first time by doctor Sweet in 1964.¹⁷ Three types of Sweet’s syndrome can be distinguished: classical Sweet’s syndrome (CSS), drug-induced Sweet’s syndrome (DISS) and malignancy-associated Sweet’s syndrome (MASS). CSS is associated with pregnancy, upper airway and gastrointestinal infections and inflammatory bowel disease like Crohn’s disease, colitis ulcerosa or other autoimmune diseases.^{3 6} Eighty per cent of the affected patients are women, ranging between the ages of 30 and 50 years, whereas in the other variants of Sweet’s syndrome this predominance is less distinctive.⁶ A wide range of drugs can induce DISS, with granulocyte colony-stimulating factor, a stimulator of the production of neutrophils, being reported as the causative drug in the majority of cases.^{14 18 19} MASS can be found as the first symptom or can be an indicator of recurrence malignancy. By combining several retrospective reviews, Cohen and Kurzrock found that approximately 21% of the cases with Sweet’s syndrome had an underlying malignancy, most commonly associated with AML, without any predominance in women.⁸ Patients with MASS with haematological malignancies have the highest rate of lesions in the head and neck region and oral mucosa, while this location is less common in patients with CSS.⁸ The exact mechanism of Sweet’s syndrome remains to be established, is probably multifactorial and differs between subtypes.² It is hypothesised that Sweet’s syndrome is a hypersensitivity reaction, initiating a cytokine cascade, to antigens of drugs, micro-organisms or tumours.^1–3 Cutaneous lesions of Sweet’s syndrome in the ear, nose and throat area are rare. To our knowledge, there is only one case report describing Sweet’s syndrome manifestation as otological lesions, accompanied with severe otalgia, dry cough and fever. The patient in the case of Saliba et al had a similar presentation as our patient, with progressive pain and clinical deterioration while given antibiotics and improvement after starting prednisone.²⁰ Otolaryngological presentation has been reported only a few times with varying symptoms.6 7 20–29

Diagnosis in our case was based on the widely accepted criteria of Su and Liu modified by von den Driesch, as defined in table 1 after excluding the possibility of an infectious disease.^{4 5} Both major criteria and at least two out of four minor criteria should be met to diagnose Sweet’s syndrome.^{4 5} Our patient met these criteria, even before we gave her systemic oral corticosteroids. The diagnosis DISS has the same major criteria, but other minor criteria as fever (over 38°C), relationship between drug intake and clinical symptoms and resolution of cutaneous lesions after cessation of the medication or starting prednisone therapy, excluding DISS as diagnosis in this case.^{5 18}

Pathology reveals that neutrophils diffusely infiltrated the dermis accompanied by oedema.^{6 30} Cutaneous lesions in Sweet’s syndrome present as erythematous nodules, are generally oedematous and might appear as translucent and vesicular papules.^{4 6 17} The distribution of the lesions is often asymmetric. Over a period of 2 days, the lesions will grow and may merge into large plaques.⁶ Diagnosing might be challenging, since there are many unusual clinical presentations of Sweet’s syndrome. The lesions might resemble bullae or appear as pustules.^31–33 Subcutaneous Sweet’s syndrome presents with erythematous nodules, particularly in the lower extremities looking similar to erythema nodosum.6 30 34 35

Diagnostic workup should consist of physical examination, laboratory tests and histopathology. Depending on the extensiveness and extracutaneous manifestations, radiology imaging should be considered. Generally, complete blood cell count with differentiation and CRP and erythrocyte sedimentation rate are taken. Urine (with pregnancy test), renal and hepatic functioning should be checked. Thyroid functioning, rheumatoid factor and tests for infection with Streptococcus can be considered. In case of clinical suspicion, further tests for excluding malignancies should be performed as well.^{3 6} In this case abscesses or infectious causes had to be ruled out before starting systemic oral corticosteroids for Sweet’s syndrome. Laboratory findings might be contradicting in MASS.³ In patients with anaemia, thrombocytopenia and leucopenia and histological proven Sweet’s syndrome, malignancy should be considered as a possible causative factor.³⁶

The induction therapy for AML, daunorubicin and antibiotics imipenem/cilastatin, have not been reported as Sweet’s syndrome inducing medication.⁶

Management of Sweet’s syndrome consists of systemic oral corticosteroids, starting with 0.5–1 mg/kg/day of prednisone in all types of Sweet’s syndrome. Symptoms should improve in 2 days.^{5 13} The prednisone can be gradually withdrawn 4–6 weeks after obtaining disease control.³⁷ Potassium iodide and colchicine can also be considered.^{38 39} In DISS, sometimes cessation of the causative drug leads to cure, without use of systemic oral corticosteroids.^{3 14 37} Single, small lesions can be treated with topical corticosteroids.^{6 37}

Recurrence of disease after cessation of prednisone therapy is common. Relapse is seen in 30% of patients with CSS and up to 70% in patients with MASS. In the latter group it might also indicate relapse of malignant disease.^{6 8} In cases without therapy, it takes several weeks to months before all the lesions are resolved.¹⁷ Complications are rarely seen, as long as no secondary infection occurs.^{6 17} It should be emphasised that necrotising Sweet’s syndrome should be considered in case of antibiotic-resistant fasciitis necroticans with negative blood cultures.⁴⁰

To our knowledge this case is relevant, since only a few reports describe the otolaryngological presentation of Sweet’s syndrome and most of them report mucosal lesions.^{7 20–29} Treatment consists of systemic oral corticosteroids based on weight and tapering based on clinical symptoms. There is no consensus to the exact amount and duration of therapy; however, Sweet’s syndrome is a dermatological diagnosis of which the otolaryngologist should be aware, because of cutaneous and mucosal manifestations in the head and neck area and the association with malignant disease. The nearly septic presentation of patients with Sweet’s syndrome may mislead the clinician, causing unnecessary use of antibiotics and delay of correct treatment with systemic oral corticosteroids. Knowledge of this syndrome is important because it may be the first indication of an underlying (recurrent) malignancy and if the dermatological manifestations occur in pregnant and/or oncological patients it may help to make the right diagnosis quickly (as in our patient).

Learning points.

• Sweet’s syndrome is a dermatological diagnosis but is prevalent in the head and neck area and therefore otolaryngologists should be aware of the condition.

• Symptoms have an acute painful onset of erythematous lesions and have no response to antibiotics.

• Sweet’s syndrome might indicate a new or recurrent malignancy.

• Treatment consists of (oral) prednisone, topical corticosteroids and adequate analgesics.

Ethics statements

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Parental/guardian consent obtained.