A case of rash…a harbinger of more serious illness?

1. A case of rash…a harbinger of more serious illness? Cassie Hajek, MD Sanford Adult Medicine September 13th, 2013

2. 32-year-old woman with rash • CC: Rash • 32-year-old woman who presented with a rash that started 5 days earlier. • She noted a tender bump on the right lower leg and thought she had bumped her leg. Over the next couple of days, she began to acquire more lesions on the lower legs. • 24-48 hours after the initial tender nodule on the leg, she started to notice lesions on her shoulders and upper trunk. These had more of a sunburn kind of quality to them. • She was out on the deck a few nights before she developed the lesions on the upper trunk, but did not recall getting any insect bites, and the lesions were not itchy • The rash progressed for 2 days, then stabilized • The lesions on the lower legs remained tender, but this improved with ibuprofen. • 2 days after the onset of the rash, she was seen in acute care and started on triamcinolone 0.5% cream which she applied to the lesions on the upper trunk with some relief • She was recently exposed to mycoplasma, but denies any other exposures.

3. ROS • Constitutional: No unexpected change in weight, no fatigue, no fevers, sweats or chills. • HEENT: Eye: No recent significant change in vision, no eye pain, redness, or discharge. Nose: She had a mild runny nose and cold-type symptoms approximately 6 weeks earlier Ear: No ear pain, no tinnitus or vertigo, no recent change in hearing. Mouth/Throat: No sore throat, no difficulty swallowing, no recent change in voice or hoarseness. Neck: No lumps or masses, no swollen glands, no recent swelling in thyroid area, no significant pain in neck. • Pulmonary: No chronic cough, sputum, or hemoptysis, no dyspnea on exertion, no wheezing, no shortness of breath • Cardiovascular: No orthopnea, no chest pain, no diaphoresis, no edema, no palpitations, no claudication symptoms. • Gastrointestinal: chronic on/off diarrhea - seems to be correlated with stress and nervousness, no abdominal pain, no melena, no hematochezia, no significant change in appetite, no nausea or vomiting • Musculoskeletal/Extremities: mild generalized arthralgias, no noted joint swelling or redness. • Heme/Allergy/Immune: No abnormal bleeding, no bruising, no night sweats, no history of DVT. • Skin/Integumentary: as mentioned in HPI • Neurologic: No chronic headaches, no seizures, no weakness, no numbness or tingling. • Psychiatric: No depression, no anxiety, no psychosis. • Endocrine: Negative for polydipsia, dry mouth, polyuria, and heat or cold intolerance. • GU: Denies abnormal vaginal bleeding, discharge or unusual pelvic pain, no dysuria, frequency or hematuria

4. Additional history Past Medical History: negative Past Surgical History: negative Medications: Nuvaring –discontinued one week prior to presentation Allergies: NKDA Family Medical History: • Mother – gastric adenocarcinoma • There is no known family history of any other cancer, connective tissue disease, inflammatory bowel disease Social History • Married • Works as a nurse in the intensive care unit • Occasional alcohol use and no tobacco or illicit drug use

5. Physical Exam • Vital signs: T = 97.8, P = 76, R = 14, BP = 104/72 • General: well-appearing woman in no acute distress • HEENT: Pupils are round and react to light. There is no eyelid pallor. Tympanic membranes are clear. Pharynx is moist and non-erythematous. Neck: Trachea is midline. There is no thyromegaly. • Lymph: There is no cervical, supraclavicular, groin or axillary adenopathy • Heart: Regular rate, no obvious murmur. PMI is not displaced. • Lungs: Lungs are clear to auscultation and percussion. • Abdomen: Abdomen is soft. Positive bowel sounds. No bruits, no masses. • Extremities: Strong pulses without edema. • Neurologic: Range of motion in the neck is appropriate. Peripheral sensation appropriate to light touch. • Musculoskeletal: Mild tenderness to palpation in bilateral elbows, no joint swelling or erythema; other joints WNL • Skin: • Upper arms, shoulders, upper back and chest had several pink, pseudo-vesicular lesionswith some that were slightly lighter centrally with erythema at the periphery but no targetoid lesions • Bilateral lower extremities: numerous dull, erythematous, tender, indurated papulesand nodules. No ulceration is appreciated. No surrounding induration or impressive erythema

6. Rash

7. Diagnostic testing • CBC: WNL • CMP: WNL • ESR: WNL • CRP: WNL • Rapid strep with reflex culture: negative • ASO titer: negative • ANA screen: negative • HIV: negative • Mycoplasma titers: negative • Peripheral smear: normal • UA: negative

8. Biopsy Results • Leg: • Dermatitis with minimal spongiosis, focal lichenoid change and vacuolar cell change with extravasated red blood cells • Biopsy lacked subcutaneous tissue component to evaluate for erythema nodosum. • Back: • Neutrophilic dermatitis • Consistent with Sweet’s syndrome

9. Sweet’s SyndromeDefinition • Acute febrile neutrophilic dermatosis • Described by Robert Sweet in 1964 • Characterized by erythematous plaques, nodules, or papules accompanied by fever, malaise, or arthralgias • Biopsy contains diffuse infiltrate of neutrophils in the papillary dermis • Female predominance

10. Sweet’s SyndromeThree Subtypes • Classic (idiopathic) • Sudden onset of the typical skin findings and histopathology without associated vasculitis • Associated symptoms may include fever, preceding infection, arthralgia, or conjunctivitis • Lab findings can include leukocytosis or elevated ESR • Malignancy-associated • Acute myelogenous leukemia – most common hematologic malignancy • Genitourinary tumors – most common solid tumor • Suspected with consistent constitutional symptoms or family history • Drug-induced • Temporal relationship between drug ingestion and onset of symptoms • Granulocyte-colony stimulating factor and trimethoprim-sulfamethoxazole

11. Sweet’s SyndromeDiagnostic Criteria Major Criteria • Abrupt onset of tender or painful erythematous or violaceous plaques or nodules • Predominantly neutrophilic infiltration in dermis without leukocytoclastic vasculitis Minor Criteria • Preceding fever or infection • Association with malignant lesion, pregnancy, inflammatory bowel disease, upper respiratory or gastrointestinal infection • Good response to systemically administered corticosteroids and not to antibiotics • Abnormal lab values: elevated ESR, leukocytosis Presence of 2 Major and 2 Minor criteria establish the diagnosis

12. Sweet’s SyndromeTreatment and Prognosis • Classical • Systemic corticosteroids for diffuses disease • Intralesional/topical corticosteroids for limited disease • Improvement begins within 48 hours of treatment • Resolution in 1-2 weeks • May require taper over several weeks • Drug-induced – discontinue offending agent • Malignancy-associated – treat underlying malignancy • Spontaneous resolution possible in weeks to months • Skin lesions generally resolve without scarring • Recurrence occurs in ~30% of patients

13. Back to our Patient… • CT Chest/Abdomen/Pelvis:Inflammatory bowel changes involving the terminal ileumwith two areas of stricture present, mild diffuse fatty infiltration of the liver with no large lymph nodes seen, minimal mesenteric fat stranding present • Colonoscopy with ileal biopsy: ileocolonic mucosa demonstrated architectural distortion, mixed lymphoplasmacytic inflammation with ulceration, and acute inflammation that was felt consistent with idiopathic inflammatory bowel disease • EGD: negative

14. Final Diagnosis and Outcome • Sweet’s Syndrome secondary to underlying Crohn’s disease • Patient initially refused systemic steroids as she did not want them to affect her colon biopsy • After colon biopsy, she was started on budesonide and azathioprine with significant improvement of her chronic diarrhea • Skin manifestations gradually resolving

15. Any Questions?

16. references • Cohen P. Sweet’s Syndrome – a comprehensive review of an acute febrile neutrophilic dermatitis. Orphanet Journal of Rare Disease. 2007; 2:34 • Rochet N, Chavan R, Cappel M, Wada D, Gibson L. Sweet syndrome: Clinical presentation, associations and response to treatment in 77 patients. J Am Acad Derm. 2013; 10:1-8

17. Sweet’s SyndromeExtracutaneous Manifestations • Bone - Acute sterile arthritis, arthralgias, focal aseptic osteitis, pigmented villonodular synovitis, sterile osteomyelitis • Central nervous system - Acute benign encephalitis, aseptic meningitis, brain SPECT abnormalities, brain stem lesions, cerebrospinal fluid abnormalities, computerized axial tomography abnormalities, electroencephalogram abnormalities, encephalitis, Guillain- Barre syndrome, idiopathic hypertrophic cranial pachymeningitis, idiopathic progressive bilateral sensorineural hearing loss, magnetic resonance imaging abnormalities, neurologic symptoms, "neuro-Sweet disease", pareses of central origin, polyneuropathy, psychiatric symptoms • Ears - Tender red nodules and pustules that coalesced to form plaques in the external auditory canal and the tympanic membrane • Eyes - Blepharitis, conjunctival erythematous lesions with tissue biopsy showing neutrophilic inflammation, conjunctival hemorrhage, conjunctivitis, dacryoadenitis, episcleritis, glaucoma, iridocyclitis, iritis, limbal nodules, ocular congestion, periocular swelling, peripheral ulcerative keratitis, retinal vasculitis, scleritis, uveitis • Kidneys - Mesangiocapillary glomerulonephritis, urinalysis abnormalities (hematuria and proteinuria) • Intestines - Intestine with extensive and diffuse neutrophilic inflammation, neutrophilic ileal infiltrate, pancolitis (culture-negative) • Liver - Hepatic portal triad with neutrophilic inflammation, hepatic serum enzyme abnormalities, hepatomegaly • Heart - Aortic stenosis (segmental), aortitis (neutrophilic and segmental), cardiomegaly, coronary artery occlusion, heart failure, myocardial infiltration by neutrophils, vascular (aorta, bracheocephalic trunk and coronary arteries) dilatation • Lung - Bronchi (main stem) with red-bordered pustules, bronchi with neutrophilic inflammation, pleural effusion showing abundant neutrophils without microorganisms, progressive pharyngeal mucosal infiltration and edema resulting in upper- airway obstruction, and chest roentgenogram abnormalities: corticosteroid-responsive culture-negative infiltratives, pulmonary tissue with neutrophilicinflammation • Mouth - Aphthous-like superficial lesions (buccal mucosa, tongue), bullae and vesicles (hemorrhagic: labial and gingival mucosa), gingival hyperplasia, necrotizing ulcerative periodontitis, nodules (necrotic: labial mucosa), papules (macerated: palate and tongue), pustules (individual and grouped: palate and pharynx), swelling (tongue), ulcers (buccal mucosa and palate) • Muscles- Magnetic resonance imaging (T1-weighted and T2-weighted) abnormalities: high signal intensities due to myositis and fasciitis, myalgias (in up to half of the patients with idiopathic Sweet's syndrome), myositis (neutrophilic), tendinitis, tenosynovitis • Spleen – Splenomegaly