What is Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)?
Acute Febrile Neutrophilic Dermatosis (AFND), also known as Sweet Syndrome or Gomm Button disease, is a skin condition that causes red patches and bumps. Along with these visible skin changes, it can also cause symptoms like fever and general discomfort or unease. This skin condition most often affects people aged between 30 and 60, and it is more common in women.
The disease can be recognized under a microscope by a high amount of a particular kind of white blood cell, called a neutrophil, in the skin. AFND is linked to many underlying health conditions, including infections, cancer, inflammatory bowel disease, autoimmune disorders, pregnancy, and certain medications.
What does it look like clinically? The skin lesions can appear as sensitive, swollen, red patches and bumps. Sometimes, these bumps can also form blisters. The most effective way to treat this disease is with a drug called prednisone. Other potential treatments include medications such as dapsone, colchicine, and potassium iodide.
What Causes Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)?
Sweet syndrome, a skin condition, can come about for three main reasons: we don’t know why (this is called idiopathic), in connection with cancer, or caused by certain medications. The symptoms of Sweet syndrome are caused by an unwarranted increase or buildup of a type of white blood cell, neutrophils, in the blood and tissues.
Idiopathic Sweet syndrome, the most common type, meets the recognized criteria for diagnosis but isn’t linked to cancer or drug exposure. Various scenarios can lead to this. For example, infections of the respiratory tract or gut can sometimes trigger Sweet syndrome, usually 1-3 weeks after the initial infection. This Syndrome can also occur in people with bowel diseases like Crohn’s disease or ulcerative colitis, and during pregnancy. However, connections with other infections or conditions like HIV, tuberculosis, chlamydia, hepatitis, or autoimmune disorders are less clear.
It is noticed that VEXAS syndrome, an autoinflammatory condition observed in adult males, shares some similarities with Sweet syndrome. Almost 90% of people diagnosed with VEXAS syndrome were found to have skin symptoms similar to those seen in Sweet syndrome.
Sweet syndrome also frequently occurs in people with cancer, specifically in children over the age of 3 and in adults. The timing of its occurrence can range from before, after, or at the same time as cancer is detected. Moreover, if a patient with a history of cancer gets Sweet Syndrome, chances of a cancer relapse could be higher. Blood cancers are more often associated with Sweet syndrome than solid tumors. Acute myeloid leukemia is the most common blood cancer associated with this syndrome.
Sometimes, certain types of drugs can cause Sweet syndrome. Granulocyte-colony stimulating factor (G-CSF) is a medication often noted in these cases. Checkpoint inhibitor treatment, a type of cancer treatment, can also result in this syndrome. It typically appears about two weeks after someone starts a new drug. If the person is given the drug again, it can trigger a recurrence of the syndrome. There are also some reports that link Sweet syndrome to antibiotics, epilepsy drugs, non-steroidal anti-inflammatories, retinoids, and diuretics, but these connections aren’t definitively proven.
Risk Factors and Frequency for Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
AFND, also known as Sweet syndrome, is a less common condition that affects people worldwide. It is four times more likely to occur in females than in males. While it can occur at any age, it is typically seen in people aged between 30 and 60. However, this gender difference isn’t as apparent in the pediatric, or child, population. No specific racial group seems to be more susceptible to Sweet syndrome.
- At least half of all patients have a recognizable underlying cause.
- Internal cancers are found in 15% to 30% of cases, with blood cancers being more common than solid organ cancers.
- About 25% of patients have an infection prior to developing the syndrome.
- About 10% of patients have been exposed to a drug that could potentially cause the syndrome.
Signs and Symptoms of Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
Sweet syndrome, also known as Acute Febrile Neutrophilic Dermatosis (AFND), is a condition typically accompanied by a fever higher than 38°C. However, in some cases associated with drug-induced influences or cancer, fever may be absent in about 10 to 20% of individuals. People with Sweet syndrome may also experience joint pain, fatigue, headaches, and muscle pain. They might have sudden tender skin bumps and nodes that are red and painful, standard signs of this syndrome. When the skin is affected, it can show:
The skin often has reddish, tender, non-itchy bumps, nodules, and patches, mainly on the face, neck, and upper body. These patches may have clustered transparent bumps giving a blister-like appearance. Sometimes there may be ulceration superficially on the skin. These clusters of lower limb nodules can resemble erythema nodosum, an inflammatory condition, and can be differentiated using microscopic imaging. The affected skin areas often feel sore or burning.
Occasionally, the symptoms may also include:
- Neutrophilic dermatosis of the dorsal hands: Described as bluish-violet or bloody bumps, bullae, and nodules on the back of the hands. It could relate to hidden or blood cancers and mimics another condition called bullous pyoderma gangrenosum.
- Subcutaneous Sweet syndrome: It bears a resemblance to red bump-like lesions on the shins. The inflammation is within the fat tissue of the skin.
- Bullous Sweet syndrome: It’s very rare, and characterized by blisters and loose bullae. It might cause an ulcer that resembles pyoderma gangrenosum and usually accompanies blood malignancies.
There are also cases resembling necrotizing fasciitis, another disease known as necrotizing Sweet syndrome. People show fever and develop red to violet skin patches. Sometimes, giant cellulitis-like Sweet syndrome has been reported with large infiltrating inflammatory patches and bullae. Also, cutaneous lesions can develop after minor skin injuries as seen in other similar skin conditions.
Oral complications are rare but about 12% of individuals with blood malignancy-related Sweet syndrome may have mouth sores, particularly on the mouth lining or tongue. Other oral issues can include blisters, gingival overgrowth, zombie mouth disease, ulcers, nodules, patches, pustules, and swelling of the tongue.
Besides skin and oral involvement, Sweet syndrome affects various organs where neutrophils, a type of immune cell, may infiltrate. These include eyes, lungs, muscles, bones, liver, spleen, heart, kidneys, brain, and intestines, producing symptoms specific to the affected part. Eye: Eye inflammation is common, presenting in 17 to 72% of individuals. Musculoskeletal system: Joint and muscle pain, arthritis are common. Other organ-specific complications may occur like encephalitis, lung inflammation, heart inflammation, hepatitis, intestinal inflammation, kidney inflammation, sterile bone infection, etc. Systemic Inflammatory Response Syndrome (SIRS), a severe body-wide inflammatory state, is also reported in association with Sweet syndrome.
Testing for Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
There isn’t a specific diagnostic test for AFND, also known as Sweet syndrome. However, certain criteria have been proposed to help diagnose this condition.
Two main conditions must be met:
* The sudden appearance of specific skin lesions
* Skin biopsy results consistent with Sweet syndrome
Alongside these major factors, at least two minor criteria should also be present:
* The presence of one of the associated infections, vaccinations, accompanying malignancies, exposure to certain drugs, or pregnancy
* A fever above 38º C
* Evidence of at least three out of four specific abnormalities in your initial lab tests: Erythrocyte sedimentation rate (ESR) above 20 mm/h; leukocytes above 8000 mm3/h; neutrophils above 70%; and high C-reactive protein (CRP)
* A significant improvement in symptoms after treatment with systemic corticosteroids or potassium iodide
If Sweet syndrome is suspected, important tests include a skin biopsy, a full blood count, ESR test, CRP test, and checks on liver and kidney function. There may also be other tests such recurrent urinary tract infections, kidney stones, autoimmune diseases, and previous damage to the urinary system.
Most people with Sweet syndrome have high leukocytes counts with neutrophilia. This is common in classic Sweet syndrome cases and in those related to cancer or drug use. Anemia and platelet disorders are often seen in Sweet syndrome cases caused by cancer or medication but seldom in classic Sweet syndrome cases. Abnormalities in full metabolic panel and urine tests might indicate liver or kidney involvement.
A thorough check of the lymph nodes, examinations of breasts and the pelvis in women, and of the prostate and testicles in men, sigmoidoscopy, and PET scans are carried out to rule out hidden cancer. However, testing for cancer should only be considered if there’s a solid reason to suspect cancer (for example, unexplained weight loss) or no other reason for a Sweet syndrome diagnosis (like recent infection, pregnancy, drug use, or diseases like inflammatory bowel disease or rheumatoid arthritis).
Treatment Options for Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
Most people with this illness need medication that affects the whole body to get it under control. However, some patients with just a few skin spots (less than 5% of their body) and no other symptoms may respond well to steroid creams. If a person has larger skin spots, they might get a cream or ointment as well as medication that treats their whole body. This approach is used often because it can help lessen the patient’s dependency on full-body drugs and make their spots heal faster.
Systemic glucocorticoids, a type of steroid medication, are often the go-to treatment for Sweet syndrome because they’ve been found to consistently and quickly help with symptoms, according to multiple studies. The fact that they’re often effective is so well-known, it’s even part of the criteria used to diagnose the illness. These glucocorticoids help regardless of whether the symptoms manifest on the skin or other parts of the body. Adults generally start with an oral version of the drug at a dose of 0.5 to 1 mg/kg per day. The symptoms usually start to get better within 48 hours, and skin spots usually go away in 1 to 2 weeks. Once the disease is under control, doctors will start to slowly lower the dosage over a period of 4 to 6 weeks.
Topical corticosteroids, strong steroid creams or ointments, are applied directly to the spots. They are usually used twice daily on the affected area for about 2 to 3 weeks. Wrapping the treated area (occlusion) can help to speed up its effect. If there are think skin patches on the body that the topical treatment isn’t helping, then the steroids can also be injected directly into the skin spots.
Colchicine, Dapsone, and Potassium Iodide are medications used less often than systemic glucocorticoids. They are used first when a patient can’t or shouldn’t be treated with systemic glucocorticoids due to other health issues they may have. If the symptoms don’t improve after 3 months of low-dose steroid treatment, other options can be added. These include dapsone, KI, and colchicine. A few other medicines, like cyclophosphamide, cyclosporine, thalidomide, clofazimine, and certain others, can also be effective, based on various studies.
Higher ‘pulse’ doses of glucocorticoids may be beneficial in treating severe cases of Sweet syndrome, or those that don’t respond well to other medications. They are given intravenously at doses ranging from 500 to 1000 mg per day for 3 to 5 days. After this treatment, the patient is put on a tapering oral glucocorticoid treatment or another systemic immunosuppressive medication. In difficult-to-treat cases, new reports suggest that rituximab, adalimumab, infliximab, tocilizumab, ustekinumab, and a type of medication called a Janus kinase (JAK) inhibitor can be beneficial.
What else can Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease) be?
In simple terms, when a patient presents with symptoms similar to Sweet syndrome— a disease causing fever, increased white blood cells, and skin problems— an infection should be one of the first possibilities the doctor considers. This is because some bacterial infections can cause very similar symptoms, including skin issues that look like Sweet syndrome. Likewise, certain bacterial, fungal, or other diseases can cause lesions resembling those of Sweet syndrome.
A particular study examined skin samples from patients with a form of Sweet syndrome associated with blood malignancies (a type of cancer). The study suggested that it’s exceptionally hard to tell whether it’s Sweet syndrome or a skin condition often found in individuals with leukemia, known as chemotherapy cutis. The study found genetic abnormalities in the skin that matched abnormalities found in earlier bone marrow biopsies in four out of five patients. This suggests that these patients might have had leukemia cutis, a specific type of skin lesion. However, more research is needed to understand if this type of analysis is helpful in differentiating between these conditions.
To diagnose Sweet syndrome, doctors primarily consider how the skin lesions look. By gathering information from the patient’s history, physical examination, lab tests, and other studies, they can differentiate it from other conditions like:
- Red, swollen plaques: skin infections; hives; drug rashes; rare skin conditions triggered by iodine or bromine; and other diseases characterized by inflamed hair follicles, small skin ulcers, skin issues that can occur when you have Crohn’s disease.
- Blisters: A type of inflammation of the blood vessels; another form of skin disorder; autoimmune diseases that cause blisters; infections causing bullous and necrotic changes.
- Nodules (a type of lesion usually associated with subcutaneous Sweet syndrome): skin infections; non-cancerous growths on the skin; inflammatory and non-inflammatory bumps; vasculitis; and cancerous conditions.
What to expect with Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
Skin lesions from AFND, also known as Sweet syndrome, usually heal on their own along with any other related symptoms. However, they can sometimes come back, often indicating the presence of underneath cancer conditions. In patients who were treated for cancer, if these skin problems return, it may signal that the cancer has come back. Unfortunately, if there are local skin complications like scarring or a condition called acquired cutis laxa, the outlook isn’t great as they rarely respond to any treatment.
In about 30% of cases, these skin issues go away on their own within three months. But it’s more common for their course to vary, with symptoms coming and going. This relapse can happen after reducing or stopping certain medication treatments, especially in patients with diseases linked to cancer. About 30% of patients with classic Sweet syndrome experience a return of their symptoms. However, if a blood cancer is present, the rate of recurrence may go up to as much as 69%.
Possible Complications When Diagnosed with Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
Although the damages usually heal with minor discoloration due to post-inflammatory effects, specific localized issues can occur. These can include scarring for ulcerative damages and tissue degradation in cases of inflammation of the fat tissue. There is also a frequent occurrence of having a loose and saggy skin condition named Marshal syndrome, a type of postinflammatory tissue breakdown.
- Minor discoloration following healing
- Scarring in cases of ulcerative damages
- Tissue degradation in cases of inflammation of the fat tissue
- Marshal syndrome, leading to saggy skin.
Preventing Acute Febrile Neutrophilic Dermatosis (Sweet syndrome, Gomm Button disease)
For individuals diagnosed with AFND (Acute Febrile Neutrophilic Dermatosis) or Sweet syndrome, it’s crucial to thoroughly explore the possibility of any hidden systemic diseases or cancer. Regular check-ups with a skin doctor are advised. For those who have received treatment for cancer, it’s important not to overlook any recurrence of skin lesions, as this could indicate that the cancer has returned.
