39: Autoinflammatory Disorders Flashcards
1
Q
What are the common clinical hallmarks of Cryopyrin-Associated Periodic Syndromes (CAPS)?
A
The common clinical hallmarks of CAPS include:
- Periodic fever
- Urticarial skin lesions
2
Q
What distinguishes Familial Cold Autoinflammatory Syndrome (FCAS) from other forms of CAPS?
A
Familial Cold Autoinflammatory Syndrome (FCAS) is characterized by:
- Mildest condition of CAPS
- Urticarial skin lesions
- Low-grade fever that develops 1-2 hours after exposure to cold temperature
- Ice cube provocation test is negative for urticaria
- Other features include arthralgia, conjunctivitis, headaches, nausea, and fatigue.
3
Q
What are the key features of Muckle-Wells Syndrome (MWS)?
A
Muckle-Wells Syndrome (MWS) is characterized by:
- Triad of urticaria, deafness, and amyloidosis
- Attacks can last 24 to 48 hours but may be continuous.
4
Q
What are the clinical features of Neonatal Onset Multisystem Inflammatory Disease (NOMID)?
A
Neonatal Onset Multisystem Inflammatory Disease (NOMID) features include:
- Persistent inflammation and diffuse erythema and fever at birth
- Chronic aseptic meningitis
- Sensory neural hearing loss
- Long bone epiphyseal overgrowth and short stature
- Amyloidosis.
5
Q
What is the role of the NLRP3 gene in Cryopyrin-Associated Periodic Syndromes (CAPS)?
A
The NLRP3 gene is crucial in CAPS as it encodes for NLRP3 (cryopyrin), which forms a multiprotein complex called the inflammasome. This inflammasome activates caspase-1, leading to the cleavage of pro-interleukin-1β and resulting in abnormal IL-1β secretion. Gain-of-function mutations in NLRP3 lead to constitutive activation of caspase-1, contributing to the inflammatory processes seen in CAPS.
6
Q
What test would be negative for a patient with familial cold autoinflammatory syndrome (FCAS) experiencing urticarial skin lesions?
A
The ice cube provocation test would be negative because systemic cold exposure, not localized cold, is required to trigger an episode.
7
Q
What is the inheritance pattern and the causative gene for Muckle-Wells syndrome (MWS)?
A
The inheritance pattern is autosomal dominant, and the causative gene is NLRP3.
8
Q
What is the underlying pathogenesis involving the inflammasome for a patient with CAPS having urticarial skin lesions unresponsive to antihistamines?
A
The inflammasome activates caspase-1, which cleaves pro-IL-1β, leading to abnormal IL-1β secretion.
9
Q
What joints are commonly affected in familial cold autoinflammatory syndrome (FCAS) and when do symptoms typically begin?
A
The hands, knees, and ankles are commonly affected. Symptoms typically begin in infancy and early childhood.
10
Q
What are the three hallmark symptoms of Muckle-Wells syndrome (MWS)?
A
The three hallmark symptoms are urticaria, deafness, and amyloidosis.
11
Q
What are the common eye and auditory complications for a patient with neonatal-onset multisystem inflammatory disease (NOMID)?
A
Common eye complications include conjunctivitis, uveitis, optic neuritis, and papilledema. Auditory complications include sensorineural hearing loss.
12
Q
What environmental condition is required to trigger an episode in familial cold autoinflammatory syndrome (FCAS)?
A
Systemic cold exposure is required to trigger an episode.
13
Q
What is the typical duration of flares in familial cold autoinflammatory syndrome (FCAS)?
A
The typical duration of flares is less than 24 hours.
14
Q
What is the inheritance pattern of familial cold autoinflammatory syndrome (FCAS)?
A
The inheritance pattern is autosomal dominant.
15
Q
What is the typical duration of attacks in Muckle-Wells syndrome (MWS)?
A
The typical duration of attacks is 24-48 hours.
16
Q
What skeletal abnormality is characteristic of neonatal-onset multisystem inflammatory disease (NOMID)?
A
Long bone epiphyseal overgrowth is characteristic of this condition.
17
Q
How does Familial Cold Autoinflammatory Syndrome (FCAS) present clinically?
A
FCAS presents with:
- Urticarial skin lesions
- Low-grade fever of short duration (1-2 hours) after exposure to cold temperature
- Negative ice cube provocation test for urticaria
- Other features may include arthralgia, conjunctivitis, headaches, nausea, and fatigue.
- Symptoms typically begin in infancy and early childhood.
18
Q
What distinguishes Muckle-Wells Syndrome (MWS) from other forms of CAPS?
A
Muckle-Wells Syndrome (MWS) is characterized by:
- A triad of symptoms: urticaria, deafness, and amyloidosis.
- Attacks can last 24 to 48 hours but may be continuous, unlike the shorter episodes seen in FCAS.
19
Q
What are the diagnostic criteria for Neonatal Onset Multisystem Inflammatory Disease (NOMID)?
A
The diagnostic criteria for NOMID include:
- Persistent inflammation and diffuse erythema and fever at birth
- Chronic aseptic meningitis
- Sensory neural hearing loss
- Long bone epiphyseal overgrowth and short stature
- Amyloidosis may also be present.
20
Q
What is the cause of Deficiency of the IL-1 Receptor Antagonist (DIRA)?
A
Due to IL1RN gene mutations leading to the absence of IL-1RA, resulting in hyperactive IL-1 signaling.
21
Q
What are the clinical features of Deficiency of the IL-1 Receptor Antagonist (DIRA)?
A
- Perinatal to several months of age onset pustular skin eruption with oral mucosal lesions.
- Failure to gain weight and painful joint swelling.
- Histopathology shows intraepidermal neutrophils and neutrophilic pustules, marked papillary dermal edema, and intense neutrophilic inflammatory infiltrate in the dermis.
22
Q
What is the management for Deficiency of the IL-1 Receptor Antagonist (DIRA)?
A
Management includes Recombinant IL-1Ra (anakinra), which is treated for life.
23
Q
What is the etiology of Deficiency of the IL-36 Receptor Antagonist?
A
Due to IL36RN gene mutation, identified as one of the causative genes of familial generalized pustular psoriasis.
24
Q
What are the clinical features of Deficiency of the IL-36 Receptor Antagonist?
A
- Recurrent and sudden onset of flares of a generalized erythematopustular skin eruption.
- High fever (40-42C), neutrophilia, and elevated hepatic acute phase proteins.
- Triggered by viral or bacterial infections, medications, menstruation, pregnancy, and withdrawal of retinoid therapy.
- Histopathology shows spongiform pustules of Kogoj with acanthosis.
25
What is the management for Deficiency of the IL-36 Receptor Antagonist?
Management includes **IL-1 and IL-17 antagonists**.
26
What is the cause of CARD14-mediated pustular psoriasis/psoriasis 2?
Due to **CARD14 mutations**, which are expressed in epidermal keratinocytes.
27
What are the clinical features of CARD14-mediated pustular psoriasis?
Features show various symptoms of common psoriasis including **plaque and pustular psoriasis**.
28
What is the management for CARD14-mediated pustular psoriasis?
Management includes **IL-1 antagonists**.
29
What is the management for CARD14-mediated pustular psoriasis?
Management includes **IL-12/IL-23 antagonist ustekinumab**.
30
What is the epidemiology of Familial Mediterranean Fever?
- **Autosomal recessive** inheritance.
- Recurrent attacks of fever and serosal inflammation.
- 80% of cases are diagnosed before 10 years of age and 90% before 20 years of age.
31
What are the clinical features of Familial Mediterranean Fever?
- Recurrent short febrile attacks with peritonitis, pleuritis, synovitis, and erysipelas-like skin lesions.
- Erysipelas-like skin lesions are well-demarcated, warm, tender, swollen, and red on the front of the lower legs, dorsum of the foot, and ankles.
- Attacks last 1-3 days and occur randomly.
- Known triggers include cold exposure, fatigue, emotional stress, and menstruation.
32
A newborn presents with pustular skin eruptions, oral mucosal lesions, and painful joint swelling. Genetic testing reveals an IL1RN mutation. What is the diagnosis and the treatment?
The diagnosis is Deficiency of the IL-1 Receptor Antagonist (DIRA). The treatment is lifelong recombinant IL-1Ra (anakinra).
33
A patient with deficiency of the IL-36 receptor antagonist (DITRA) has recurrent erythematopustular skin eruptions triggered by infections. What is the causative gene and the histopathological finding?
The causative gene is IL36RN. The histopathological finding is spongiform pustules of Kogoj with acanthosis.
34
A patient with CARD14-mediated pustular psoriasis has plaque and pustular psoriasis. What pathway is upregulated, and what is the treatment?
The NF-κB pathway is upregulated. The treatment is IL-12/IL-23 antagonist ustekinumab.
35
A patient with deficiency of the IL-1 receptor antagonist (DIRA) has intense neutrophilic inflammatory infiltrate in the dermis. What is the clinical course if untreated?
The clinical course involves severe inflammatory response syndrome and neonatal death if untreated.
36
A patient with familial Mediterranean fever (FMF) has peritonitis and pleuritis. What triggers are known to precipitate attacks?
Known triggers include cold exposure, fatigue, emotional stress, and menstruation.
37
A patient with deficiency of the IL-36 receptor antagonist (DITRA) has high fever and neutrophilia. What triggers are associated with flares?
Triggers include viral or bacterial infections, medications, menstruation, pregnancy, and withdrawal of retinoid therapy.
38
A patient with CARD14-mediated pustular psoriasis has increased IL-8 and IL-36 production. What cell type is primarily involved in this upregulation?
Epidermal keratinocytes are primarily involved in this upregulation.
39
A patient with familial Mediterranean fever (FMF) has erysipelas-like skin lesions. What histopathological findings are characteristic of these lesions?
Histopathological findings include edema of the superficial dermis and perivascular and interstitial neutrophilic infiltrate without vasculitis.
40
A patient with deficiency of the IL-36 receptor antagonist (DITRA) has elevated hepatic acute phase proteins. What is the primary cytokine involved in the pathogenesis?
The primary cytokine involved is IL-36.
41
A patient with CARD14-mediated pustular psoriasis is treated with ustekinumab. What cytokines does this treatment target?
Ustekinumab targets IL-12 and IL-23.
42
A patient with deficiency of the IL-1 receptor antagonist (DIRA) has failure to gain weight. What is the histopathological finding in the skin?
Histopathological findings include intraepidermal neutrophils and neutrophilic pustules, marked papillary dermal edema, and intense neutrophilic inflammatory infiltrate in the dermis.
43
A patient with deficiency of the IL-36 receptor antagonist (DITRA) has generalized erythematopustular skin eruptions. What is the histopathological hallmark?
The histopathological hallmark is spongiform pustules of Kogoj with acanthosis.
44
A patient with CARD14-mediated pustular psoriasis has increased CCL20 production. What signaling pathway is involved in this upregulation?
The NF-κB signaling pathway is involved in this upregulation.
45
A patient with deficiency of the IL-1 receptor antagonist (DIRA) has neonatal death. What genetic test confirms the diagnosis?
Genetic testing for IL1RN mutations confirms the diagnosis.
46
How does the management of Deficiency of the IL-1 Receptor Antagonist (DIRA) differ from that of Deficiency of the IL-36 Receptor Antagonist?
- **DIRA Management:** Recombinant IL-1Ra (anakinra) is used and is treated for life.
- **IL-36 Receptor Antagonist Management:** Involves IL-1 and IL-17 antagonists.
47
What triggers the flares in patients with Deficiency of the IL-36 Receptor Antagonist?
- Viral or bacterial infections
- Medications
- Menstruation
- Pregnancy
- Withdrawal of retinoid therapy
48
What are the common clinical features of Familial Mediterranean Fever (FMF)?
- Recurrent short febrile attacks with peritonitis, pleuritis, synovitis, and erysipelas-like skin lesions.
- Erysipelas-like skin lesions are well-demarcated, warm, tender, swollen, and red on the front of the lower legs, dorsum of the foot, and ankles.
- Attacks last 1-3 days and occur randomly.
49
What is the genetic basis of CARD14-mediated pustular psoriasis?
- CARD14 mutations lead to increased NF-KB activity, which upregulates IL-8, IL-36, and CCL20, contributing to the pathogenesis of the disease.
50
What are the diagnostic criteria for recurrent fever-associated erysipelas-like skin lesions?
- Recurrent episodes of fever-associated erysipelas-like skin lesions with abdominal, pleural, and joint pains lasting 1-3 days
- Increase in ESR, CRP, SAA, fibrinogen, and low-grade neutrophils
- Genetic testing for MEFV
51
What is the prognosis for patients with this condition?
- It is a **lifelong disease** and **cannot be cured**.
- The most severe complication is **secondary amyloidosis**, which can lead to **renal failure**.
52
What are the management options for this condition?
1. **Colchicine**
2. **IL-1 antagonists**, including canakinumab, are considered second line therapy.
53
A patient with familial Mediterranean fever (FMF) has erysipelas-like skin lesions and recurrent febrile attacks. What is the most severe complication, and how is it managed?
The most severe complication is secondary amyloidosis leading to renal failure. It is managed with colchicine and IL-1 antagonists like canakinumab.
54
A patient with familial Mediterranean fever (FMF) has abdominal pain and joint pains lasting 1-3 days. What laboratory findings support the diagnosis?
Laboratory findings include increased ESR, CRP, SAA, fibrinogen, and low-grade neutrophils.
55
What are the key diagnostic criteria for a condition characterized by recurrent fever-associated erysipelas-like skin lesions?
- Recurrent episodes of fever-associated erysipelas-like skin lesions with abdominal, pleural, and joint pains lasting 1-3 days
- Increase in ESR, CRP, SAA, fibrinogen, and low-grade neutrophils
- Genetic testing for MEFV
56
What is the prognosis for patients diagnosed with a lifelong disease that cannot be cured, and what is the most severe complication associated with it?
- The disease is lifelong and cannot be cured.
- The most severe complication is secondary amyloidosis leading to renal failure.
57
What are the first-line and second-line management options for a condition associated with recurrent fever and skin lesions?
1. **First-line management**: Colchicine
2. **Second-line management**: IL-1 antagonists including canakinumab.
58
What is the inheritance pattern of Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
HIDS is an autosomal recessive disorder.
59
What are the common clinical features of Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
Common clinical features include high, spiking fever preceded by chills, abdominal pain, diarrhea, vomiting, headache, joint pain, cervical lymphadenopathy, and skin lesions such as widespread erythematous macules and papules.
60
What is the typical age of onset for Mevalonate Kinase Deficiency (MKD)?
The typical age of onset for MKD is 5 years old.
61
What is the management goal for patients with Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
The management goal is to alleviate symptoms and improve quality of life.
62
What are the two mechanisms involved in the pathogenesis of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)?
The two mechanisms are: 1. Impaired TNFR shedding from the cell membrane, leading to reduced ligand binding and defective apoptotic signaling. 2. Abnormal TNFR1 oligomerization, which sensitizes cells to stimuli, enhancing activation of mitogen-activated protein kinases and increasing synthesis of proinflammatory cytokines.
63
What is the clinical course and prognosis for patients with Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
The clinical course for HIDS is generally associated with a long-term good prognosis, and amyloidosis is rare.
64
What are the differential diagnoses for Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
Differential diagnoses include appendicitis, Familial Mediterranean Fever (FMF), TRAPS, MWS, and Behcet's Disease.
65
A 5-year-old child presents with recurrent high-grade fevers, abdominal pain, and erythematous macules. What is the most likely diagnosis, and what is the first-line treatment?
The most likely diagnosis is Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS). First-line treatment includes NSAIDs.
66
A patient with a history of autosomal dominant inheritance presents with recurrent fever, myalgia, and periorbital edema. Genetic testing confirms TNFRSF1A mutation. What is the diagnosis, and what are the two mechanisms of pathogenesis?
The diagnosis is Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS). The two mechanisms of pathogenesis are impaired TNFR shedding and abnormal TNFR1 oligomerization.
67
A patient with HIDS has acral skin lesions. What types of skin lesions are most commonly seen?
The most common skin lesions are widespread erythematous macules and papules.
68
A patient with HIDS presents with severe neurologic impairment and growth retardation. What severe form of the disease might this indicate?
This indicates Mevalonic aciduria, a severe form of Mevalonate Kinase Deficiency (MKD).
69
A patient with HIDS has recurrent episodes of fever lasting 3-7 days. What is the typical recurrence interval for these episodes?
The typical recurrence interval is every 4-8 weeks.
70
A patient with TRAPS has conjunctivitis and erythematous patches. What is the underlying genetic mutation?
The underlying genetic mutation is in the TNFRSF1A gene.
71
A patient with HIDS has elevated ESR, CRP, and neutrophilic leukocytosis. What is the definitive diagnostic test?
The definitive diagnostic test is genetic testing.
72
What are the clinical features of Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
The clinical features of HIDS include: - High, spiking fever preceded by chills - Abdominal pain, diarrhea, vomiting - Headache, joint pain, cervical lymphadenopathy - Skin lesions such as widespread erythematous macules and papules, urticaria, annular erythema, erythematous nodules, and petechiae - Onset typically occurs at 5 years of age - Episodes last 3-7 days and recur every 4-8 weeks - 50% of patients may have oral aphthous ulcers and/or genital ulceration.
73
What is the management strategy for patients with Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
The management strategy for HIDS includes: 1. Goal: Alleviate symptoms and improve quality of life 2. Medications: - NSAIDs for symptom relief - Oral steroids for patients refractory to NSAIDs - Colchicine is NOT effective - Anakinra, Etanercept, and Canakinumab (1st FDA approved) as treatment options.
74
What are the key differences in the clinical features between Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS) and Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)?
| Feature | Hyperimmunoglobulinemia D (HIDS) | Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) |
|---------|----------------------------------|--------------------------------------------------|
| Onset | Typically at 5 years of age | Presents before 10 years of age |
| Fever Episodes | 3-7 days, recur every 4-8 weeks | Recurrent high-grade fever |
| Skin Lesions | Widespread erythematous macules and papules | Discrete erythematous macules and papules, erythematous patches, edematous or urticarial plaques |
| Other Symptoms | Abdominal pain, diarrhea, vomiting, joint pain | Myalgia, serositis, periorbital edema, conjunctivitis |
75
What is the genetic basis of Mevalonate Kinase Deficiency (MKD) associated with Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
Mevalonate Kinase Deficiency (MKD) is caused by mutations in the MVK gene, which encodes the enzyme mevalonate kinase. This deficiency leads to the accumulation of mevalonic acid, resulting in the clinical manifestations of HIDS.
76
What are the diagnostic criteria for Hyperimmunoglobulinemia D with Periodic Fever Syndrome (HIDS)?
The diagnostic criteria for HIDS include: 1. Clinical suspicion based on symptoms 2. Genetic testing to confirm the diagnosis 3. Laboratory findings: - Elevated ESR, CRP, and neutrophilic leukocytosis - Most typical finding: elevated serum IgD (not specific for HIDS) - Increased IgA in 80% of HIDS cases.
77
What are the clinical features of Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)?
- Recurrent high-grade fever
- Myalgia, serositis, periorbital edema, conjunctivitis
- Skin lesions: discrete erythematous macules and papules, erythematous patches, edematous or urticarial plaques
- Onset typically before 10 years of age
- Episodes last 3-7 days, recovering and recurring every 4-8 weeks.
78
What are the two mechanisms by which mutations in the TNFRSF1A gene affect patients with TRAPS?
1. Impaired TNFR shedding from the cell membrane, leading to reduced ligand binding and defective apoptotic signaling. 2. Abnormal TNFR1 oligomerization, which sensitizes cells to stimuli such as lipopolysaccharide, enhancing activation of mitogen-activated protein kinases and increasing synthesis of proinflammatory cytokines.
79
What are the clinical features associated with Haploinsufficiency of A20 (HA20)?
- Fever
- Bipolar ulceration of mucosal surfaces
- Skin lesions: erythematous papules, pseudofolliculitis, erythema nodosum-like lesions
- Uveitis
- Polyarthritis
80
What is the management for Otulipenia/OTULIN-related autoinflammatory syndrome (ORAS)?
- Etanercept
- Anakinra
81
What are the diagnostic criteria for Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE)?
- Chronic anemia
- Elevated ESR & CRP
- Elevated IgG, IgE, IgA, and IgM
- Genetic testing for PSMB8
- Histopathology: dense dermal infiltration of mononuclear cells, histiocytes, eosinophils, and neutrophils in the perivascular and interstitial areas of dermis and subcutaneous fat.
82
What are the epidemiological characteristics of Otulipenia/OTULIN-related autoinflammatory syndrome (ORAS)?
- Autosomal recessive disorder
- Caused by loss-of-function mutations in OTULIN.
83
What are the clinical implications of the findings in Proteasome-associated autoinflammatory syndrome (PRAAS)?
- Lifelong disease with fluctuations in disease severity
- Life expectancy can be reduced due to systemic inflammation.
84
A patient with TRAPS develops proteinuria. What is the underlying complication, and how does it occur?
The complication is amyloidosis, caused by renal deposition of Serum Amyloid A (SAA), leading to proteinuria and potential renal failure.
85
A patient presents with recurrent fevers, oral and genital ulcers, and erythematous papules. Genetic testing reveals a TNFAIP3 mutation. What is the diagnosis, and what is the recommended treatment?
The diagnosis is Haploinsufficiency of A20 (HA20). Recommended treatments include Colchicine, Anakinra, and Etanercept.
86
A child presents with prolonged fever, rash, and developmental delay. Skin biopsy shows neutrophilic dermatitis and panniculitis. What is the diagnosis, and what mutation is responsible?
The diagnosis is Otulipenia/OTULIN-related autoinflammatory syndrome (ORAS). The responsible mutation is in the OTULIN gene.
87
A child with ORAS has progressive lipodystrophy. What other systemic symptoms are commonly seen?
Other systemic symptoms include prolonged fever, rash, arthralgia, and diarrhea.
88
A patient with CANDLE syndrome has basal ganglia calcification. What other systemic features might be present?
Other systemic features include lymphadenopathy, hepatosplenomegaly, and short stature.
89
A patient with CANDLE syndrome has long, clubbed fingers. What other dermatological features might be present?
Other dermatological features include pernio-like and nodular erythema-like eruptions.
90
A patient with TRAPS has amyloidosis. What percentage of TRAPS patients develop this complication?
Approximately 10-15% of TRAPS patients develop amyloidosis.
91
A patient with HA20 has pathergy. What is the clinical significance of this finding?
Pathergy is a diagnostic clue that helps differentiate HA20 from other autoinflammatory disorders.
92
A patient with ORAS has erythematous and pustular rash. What is the histopathological finding on skin biopsy?
Skin biopsy shows neutrophilic dermatitis and panniculitis.
93
A patient with recurrent fever and pernio-like eruptions is found to have elevated IgG, IgE, IgA, and IgM. Genetic testing confirms PSMB8 mutation. What is the diagnosis, and what is the prognosis?
The diagnosis is Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE). The prognosis involves lifelong disease with fluctuating severity and reduced life expectancy due to systemic inflammation.
94
A patient with TRAPS has a histopathology report showing perivascular dermal infiltrate of lymphocytes and monocytes. What is the significance of this finding?
This nonspecific histopathology finding supports the diagnosis of TRAPS but requires correlation with clinical and genetic testing.
95
A patient with HA20 presents with erythema nodosum-like lesions and pathergy. What other condition does this presentation resemble?
This presentation resembles Behçet disease.
96
A child with CANDLE syndrome has periorbital erythema and edema, myositis, and hepatosplenomegaly. What genetic mutation is responsible, and what is the histopathological finding?
The responsible mutation is in the PSMB8 gene. Histopathology shows dense dermal infiltration of mononuclear cells, histiocytes, eosinophils, and neutrophils.
97
A patient with HA20 is treated with Colchicine. What other treatments can be considered if symptoms persist?
Other treatments include Anakinra and Etanercept.
98
A child with ORAS has a skin biopsy showing neutrophilic dermatitis. What is the molecular mechanism underlying this condition?
The molecular mechanism involves loss-of-function mutations in OTULIN, leading to increased linear ubiquitination and elevated NF-kappa B–dependent proinflammatory transcripts.
99
A patient with CANDLE syndrome has elevated ESR, CRP, and chronic anemia. What autoimmune features might also be present?
Autoimmune features may include antinuclear antibodies and other autoantibodies.
100
A patient with TRAPS is treated with NSAIDs but remains symptomatic. What is the next step in management?
The next step in management includes high-dose steroids or biologics like Etanercept, Anakinra, or Canakinumab.
101
A patient with HA20 has uveitis and polyarthritis. What genetic mutation is responsible for this condition?
The responsible mutation is in the TNFAIP3 gene.
102
What are the clinical features associated with Haploinsufficiency of A20 (HA20) and how do they relate to the diagnosis?
Clinical Features of HA20: - Fever - Bipolar ulceration of mucosal surfaces (oral and genital) - Skin lesions: erythematous papules, pseudofolliculitis, erythema nodosum-like lesions, pathergy - Polyarthritis. Diagnosis: Clinical findings and genetic testing.
103
What is the responsible mutation in Haploinsufficiency of A20 (HA20)?
The responsible mutation is in the TNFAIP3 gene.
104
What are the clinical features associated with Haploinsufficiency of A20 (HA20)?
Clinical features include fever, bipolar ulceration of mucosal surfaces (oral and genital), skin lesions (erythematous papules, pseudofolliculitis, erythema nodosum-like lesions, pathergy), and polyarthritis.
105
How is the diagnosis of Haploinsufficiency of A20 (HA20) made?
Diagnosis is made through clinical findings and genetic testing for TNFAIP3 gene mutations.
106
How does the management of Otulipenia/OTULIN-related autoinflammatory syndrome (ORAS) differ from CANDLE?
Management of ORAS includes medications like Etanercept and Anakinra, while CANDLE has no effective treatment, with options providing only transient improvement.
107
What are the implications of elevated ESR, CRP, and leukocytosis in autoinflammatory disorders?
These findings indicate systemic inflammation, assist in differential diagnosis of conditions like FMF, HIDS, sJIA, BD, and MWS, and help assess disease activity and treatment response.
108
What are the key histopathological findings in Proteasome-associated autoinflammatory syndrome (PRAAS)?
Key findings include dense dermal infiltration of mononuclear cells, histiocytes, eosinophils, and neutrophils in perivascular and interstitial areas.
109
Where are the lesions typically located in a patient with Blau Syndrome?
The lesions are typically located on the trunk and extremities.
110
When do cutaneous manifestations typically appear in PAPA syndrome?
Cutaneous manifestations typically appear at the time of puberty.
111
What diagnostic test can confirm the underlying genetic mutation in Blau Syndrome?
Genetic testing for NOD2 can confirm the mutation.
112
What is the diagnosis for a child with granulomatous dermatitis and painless polyarthritis confirmed by NOD2 mutation?
The diagnosis is Blau Syndrome/Early-Onset Sarcoidosis, with uveitis as the most challenging manifestation.
113
What is the diagnosis for a teenager with poorly healing ulcers, nodulocystic acne, and arthritis with PSTPIP1 mutation?
The diagnosis is Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) syndrome, with joint destruction as the main long-term complication.
114
What cells compose the noncaseating granulomas in Blau Syndrome?
The granulomas are composed of histiocytes and multinucleated giant cells located in the upper dermis.
115
What potential side effect should be monitored in a patient with PAPA syndrome treated with high-dose steroids?
High-dose steroids can worsen acne, a key feature of PAPA syndrome.
116
What is the underlying cause of photophobia and blurred vision in a patient with Blau Syndrome?
The symptoms are caused by uveitis, a challenging manifestation of Blau Syndrome.
117
What is the characteristic appearance of ulcers in a patient with PAPA syndrome?
The ulcers have poorly healing, undermined edges.
118
What are the common skin manifestations associated with SAPHO syndrome?
Common skin manifestations include pustular psoriasis (PPP) and severe acne (e.g., acne conglobata, acne fulminans, hidradenitis suppurativa).
119
What is the typical age of onset for SAPHO syndrome?
The typical age of onset is middle-aged adults, but it can occur at any age, including childhood.
120
What are the osteoarticular manifestations of SAPHO syndrome?
Osteoarticular manifestations include oligoarthritis affecting sternocostal joints, sternoclavicular joints, sacroiliac joints, knees, and ankles, as well as osteitis affecting the anterior chest wall.
121
What is the first line treatment for SAPHO syndrome?
The first line treatment includes NSAIDs (Non-Steroidal Anti-Inflammatory Drugs).
122
What diagnostic methods are used for SAPHO syndrome?
Diagnostic methods include clinical evaluation, radiologic imaging (radiography, ultrasonography, CT, MRI), and histologic findings from bone biopsy.
123
What are the differential diagnoses for SAPHO syndrome?
Differential diagnoses include infectious osteomyelitis and bone tumors such as Ewing sarcoma and osteoblastoma.
124
What imaging modalities can confirm the diagnosis of SAPHO syndrome?
Imaging modalities include radiography, ultrasonography, CT, MRI, and bone scintigraphy.
125
What is the diagnosis for a middle-aged adult with severe acne, oligoarthritis, and osteitis affecting the anterior chest wall?
The diagnosis is SAPHO syndrome, with NSAIDs as the first-line treatment.
126
What advanced treatments can be considered for a patient with SAPHO syndrome unresponsive to NSAIDs?
Advanced treatments include Anakinra and Etanercept for refractory cases.
127
What histopathological findings are expected in a bone biopsy for SAPHO syndrome?
Bone biopsy reveals sterile osteomyelitis with abscesses, progressively replaced by sclerotic bone trabeculae and marrow fibrosis.
128
What other skin condition is commonly associated with severe acne conglobata in SAPHO syndrome?
Palmoplantar pustulosis (PPP) is commonly associated with SAPHO syndrome.
129
What are the key clinical features of SAPHO syndrome?
Key features include skin manifestations (PPP, severe acne) and osteoarticular manifestations (oligoarthritis, osteitis). Symptoms typically appear within 2 years of each other.
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What diagnostic methods are used to confirm SAPHO syndrome and what findings are expected?
Diagnostic methods include clinical evaluation, radiologic imaging, and histologic findings from bone biopsy revealing abscesses replaced by sclerotic bone.
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What are the management strategies for SAPHO syndrome?
Management includes NSAIDs, corticosteroids, topical treatments, and for refractory cases, Anakinra or Etanercept.
