A Case Of Bad Itch

Dr . Zareen Mohamed Consultant Allergist

Mehta Hospitals

Patient Presentation

• A 45 year gentleman presented to our allergy clinic with symptoms of hives and intense pruritis

for the past 3 months.• He complained that the rash and itching is more

prominent in the night .He complains of considerable distress from the rash which he describes it as of burning quality

• He also complains of frequent thirst and dryness of skin despite adequate fluid intake

Patient presentation

• The hives are present for the past three to four months and are partially controlled with certizine 10 mg q.h.s.

• No history of exposure to new medication, dietary supplements, naturopathic medicines, cosmetics or recent travel

• No history of any significant viral or bacterial infection prior to the onset of hives

Patient presentation

Presentation negative for - Fever - Chills - Weight loss- Fatigue - Joint pain - Abdominal complaints / any other systemic

complaints

Past Medical History

• The patient did not complain of similar episodes in the past

• No significant past medical or surgical history

• No family history of Urticaria • Not a Hypertensive or diabetic• Family history insignificant for autoimmune

disease

Clinical Examination

• Vitals Normal • Review of systems – Normal • No external skin rash

Investigations

CBC- NormalHb/TC/DC/ESR- NormalLiver function test/ Renal function test- NormalNormal urine analysisFood Allergy panel for serum specificantibodies by allergy prick test - NormalNormal Thyroid function with no anti thyroid antibodies

Patient Presentation• The patient was advised to change to non sedating antihistamines

and advised to follow up in 3 weeks for review

• The patient visited the clinic after 2 weeks with increasing pruritus and decreasing exercise tolerance

• O/E: No hives, dryness of skin noted Non tender firm lymph nodes noted in the cervical region

• He gave a similar history of lymph node swelling one year back when he underwent FNAC of his lymph nodes , and was treated symptomatically for Kikuchi fujimoto diease

Investigations

• Peripheral smear – Normal• Serum calcium – 9.2 mg/dl• Antinuclear antibodies – Negative at 1: 40

dilution• CXR – Lungs - small calcific foci at bilateral

apex. Possibly healed granuloma.• Serum LDH- Normal • Serum Uric acid – 5.4 mg/dl• Ultrasound of the neck

Investigations

USG NECK • Thyroid –no nodes/cyst/calcification

• 3 or 4 enlarged lymph nodes seen in Rt side of neck largest measures 2.6 * 0.6 cm, multiple enlarged , edematous ,oval or spherical shaped lymph nodes is seen in left side of neck and supraclavicular region, largest measures 2.9* 1.5 cm.

USG NECK

• Few nodes show small cystic necrosis within lymph nodes. Few nodes show punctata echogenic focus within lymphatic node with calcification or caseation necrosis with no increased vascularity within it

Imp: Bilateral cervical lymphadentis - suggested fnac/hpe correlation.

Investigations

CXR LUNG• small calcific foci at bilateral apex.

Possibly healed granuloma.

• TISSUE BIOPSY/PET SCAN/ IHC – all suggestive of Hodgkin’s Lymphoma stage 11 a

Hodgkin’s lymphoma• - Hodgkin lymphoma (formerly called

Hodgkin's disease) is a group of cancers characterized by Reed-Sternberg cells in an appropriate reactive cellular background.

-Hodgkin lymphoma has a bimodal age distribution with one peak in the 20s and 30s, and a second peak over the age of 50.

Symptoms of hodgkin’s lymphoma:

• General symptoms:I.Fever II.Weight lossIII.Loss of appetiteIV.Night sweatsV.PruritusVI.lethargy

Hodgkin’s Lymphoma and skin

• Pruritus can be a symptom of a distinct dermatologic condition or of an occult underlying systemic disease.

• Hodgkin lymphoma is the malignant disease most strongly associated with pruritus, which affects up to 30 percent of patients with the disease.

Hodgkin’s Lymphoma and Skin

• Pruritus can precede the clinical presentation of lymphoma by up to five years and is often the presenting symptom

• A brief review of the literature demonstrates that the occurrence of hives as a presenting manifestation of Hodgkin's disease is uncommon though pruritus is known to be a frequent symptom of lymphomas in general.

urticaria

Hodgkin’s Lymphoma and Skin

• Skin lesions — A variety of skin lesions have been associated with Hodgkin lymphoma.

• These include ichthyosis, acrokeratosis (Bazex syndrome), erythema multiforme, erythema nodosum, necrotizing lesions, hyperpigmentation, and skin infiltration

ichthyosis

Erythema nodosum

URTICARIA

• Urticaria involves intensely pruritic, raised wheals, with or without edema of the deeper cutis.

• It is usually a self-limited, benign reaction, but can be chronic.

• Rarely, it may represent serious systemic disease or a life-threatening allergic reaction (around 1%)

Urticaria • Triggers often can be identified in patients with

acute urticaria, although a specific trigger is found in only 10 to 20 percent of chronic cases.

• Common triggers include allergens, food pseudoallergens

• Urticaria can be caused by allergic reactions to medications, especially antibiotics, and through direct mast cell degranulation by some medications, including aspirin, nonsteroidal anti-inflammatory drugs, radio-contrast dye, muscle relaxants, opiates, and vancomycin.

Urticaria

• Systemic disease is a relatively rare cause, with the exception of Hashimoto disease; thyroid autoimmunity may be associated with up to 30 percent of chronic urticaria cases

• Systemic illnesses that have been associated with urticaria or angioedema include mastocytosis, systemic lupus erythematosus, vasculitis, hepatitis, and lymphoma.

Urticaria

• A wide variety of different infections, including hepatitis , infectious mononucleosis , Helicobacter pylori infection , dental infections, sinusitis and urinary tract infections, have all been implicated as causing urticaria.

Kikuchi fujimoto disease• Kikuchi-Fujimoto disease is a histiocytic

necrotizing lymphadenitis which is a rare and benign condition

• Can mimic other diseases such as lymphoma, tuberculous adenitis, metastatic disease, SLE, cat scratch disease and infectious mononucleosis

• pathogenesis is unclear but is believed to be an immune response of T cells and histiocytes to an unknown inciting agent such as EBV, HHV 6 & 8, HIV, toxoplasma and paromyxoma viruses

Kikuchi fujimoto disease

Yoshino T, Mannami T et al reported on Two cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) following diffuse large B-cell lymphoma.

Kikuchi fujimoto disease• Krueger GR, Huetter ML, Rojo J, Romero M,

Cruz-Ortiz H et al reported on Human herpesviruses HHV-4 (EBV) and HHV-6 in Hodgkin's and Kikuchi's diseases and their relation to proliferation and apoptosis.

• Menasce LP, Banerjee SS, Edmondson D, Harris M et al reported on Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease): continuing diagnostic difficulties

Kikuchi fujimoto disease• Immunohistochemical monitoring of

plasmacytoid cells in lymph node sections of Kikuchi-Fujimoto disease by a new pan-macrophage antibody Ki-M1P These results may represent an additional argument favoring the histiocytic origin of plasmacytoid cells.

• Additionally, they may point to an immunohistochemical tool that facilitates the differential diagnosis between Kikuchi-Fujimoto disease, especially in early stages of the disease, and malignant lymphoma.

Pruritus and internal disease

Cholestatic pruritus

• Primary biliary cirrhosis, primary sclerosing cholangitis, B and C viral hepatitis, autoimmune hepatitis, carcinoma of bile ducts, alcoholic cirrhosis

• Pruritus is caused by the bile acids in the blood (cholemia) or skin

• Commonly treatment is with phototherapy, cholestyramine, plasmapheresis

Pruritus in chronic renal failure and dialysis patients

• uremic pruritus is due to Iron deficiency, release of histamine, disturbances of calcium-phosphate metabolism, secondary hyperparathyroidism, proliferation of mast cells in the skin, hypervitaminosis A

• Treatment of renal pruritus is based on the use of ultraviolet therapy, emollients, activated charcoal, cholestyramine, and phosphate binding agents. Sometimes parathyroidectomy is necessary for reduction of itching

Pruritus in hematologic diseases

• In polycythemia vera, where overproduction of all three hematopoietic cell lines occurs, itching may appear following contact with water or after a hot bath

• It is caused by release of histamine and other substances from an increased number of blood basophils; antihistamines do not relieve from this symptom, and currently the most effective method to treat this kind of pruritus is the use of salicylates, photochemotherapy or interferon-a

Pruritus in hematologic diseases

• In older patients the cause of pruritus can be a malignant tumour, that may also lead to anemia.

• Pruritus may also be present in patients with hemochromatosis where the levels of iron in blood and tissues are elevated

Endocrine pruritus

• Pruritus is present occasionally in diabetics. • Itch may be generalized or more frequently

localized on the scalp, the genitalia or the perianal area.

• It may be attributed to a concomitant candidiasis or, more often, to poor control of diabetes, sometimes expressed as elevated glycosylated hemoglobin blood levels

Endocrine pruritus

• The pruritus in diabetes mellitus may also be linked to neuropathy, dry skin, and drug administration. Treatment consists in the control of diabetes, and the use of antifungal agents

Endocrine pruritus

• Pruritus and even chronic urticaria may be associated with the presence of thyroid autoimmunity and antibodies against several thyroid components such as are thyreoglobulin, and TSH receptor. Levothyroxin is the appropriate treatment in such cases.

• Hormonal deficit in women in the postmenopausal period may provoke vulvar pruritus

Pruritus and malignancy

• Carcinoma of the lung, stomach, colon, prostate, breast and pancreatic rarely have been associated with generalized pruritus

• Pruritus is an important symptom in patients with different forms of mastocytosis: solitary mastocytoma, urticaria pigmentosa, systemic mastocytosis

Pruritus and malignancy

• In carcinoid syndrome pruritus is sometimes associated with flushing. The pruritus is elicited by serotonin and treatment with antiserotonin drugs alleviates the symptom.

• The association of pruritus with tumors is not always understood. It may be triggered by immunological mechanisms, toxic metabolites, iron deficiency, and dry skin

Drug-induced pruritus

• Morphine, opioids, angiotensine converting enzyme inhibitors, analgesics, vitamin A, contrast media, gold, chloroquine and sulfonamides are among the drugs that may induce pruritus

Pruritus and Hodgkin’s Disease• About 30% of the patients with Hodgkin’s

disease feel itchy. Pruritus can be an early or presenting complaint.

• It can be very severe, and this may imply a worse prognosis. Hodgkin’s pruritus improves after radiation therapy or chemotherapy

• Released from circulating basophils histamine and leukopeptidase - from white blood cells - may trigger pruritus associated with lymphomas and leukemias

In conclusion

• The most important tool for treatment of the pruritus in internal diseases is the specific treatment of the concrete internal disease, which should not be underestimated