Keywords
Chronic myeloid leukemia - erectile dysfunction - imatinib - priapism
Introduction
For more than a century, priapism has been reported to be associated with leukemia.[1] Hematological disorders constitute the etiology of almost 20% of cases of priapism.
It is most commonly seen in sickle cell disease (40%–50% of cases) followed by leukemia
(5% of cases). The most common leukemia presenting with priapism is chronic myeloid
leukemia (CML), and the incidence varies from 2% to 25%.[2],[3],[4] Priapism has also been reported at presentation in acute myeloid leukemia and multiple
myeloma.[4],[5] Due to social stigma or shyness, the real incidence of priapism in our population
is difficult to estimate. Since the successful development of tyrosine kinase inhibitors
(TKIs), the life expectancy of CML-chronic phase (CML-CP) has been comparable to the
healthy population, and the importance of priapism has further magnified, as the long-term
outcome and fertility issues are not very well known.
Case Report
A 24-year-old previously healthy gentleman presented with painful erection of the
penis for 5-day duration. He was married for 1 year and was sexually active. There
was no history of any injury, illicit drug use, or sexual intercourse before the occurrence
of priapism. He had a history of multiple such episodes which remitted on their own
after a couple of hours which he had attributed to his newly married life and sexual
activity. He denied any history of constitutional symptoms. His examination revealed
“Triple P” (pallor – pale conjunctiva, palpable spleen – 8 cm below the left costal
margin, and priapism – rigid and edematous penile shaft with soft glans penis) [Figure 1]. His hearing and visual acuity were normal along with no evidence of papilledema.
There was no evidence of perineal injury, and rest of the examination was unremarkable.
His blood investigation showed hemoglobin 107 × 109/L, white blood cell (WBC) 207
× 109/L, and platelet count 545 × 109/L. Peripheral blood smear showed immature cells
of granulocytic lineage with 3% blasts. Biochemical profile was normal. Bone marrow
examination was consistent with CML-CP, and real-time-polymerase chain reaction for
breakpoint cluster region–Abelson murine leukemia (BCR-ABL) transcript was positive.
Penile biopsy revealed infiltration by leukemia [Figure 2].
Figure 1: Clinical image of the persistently erected, edematous penis
Figure 2: (a) Penile biopsy (H and E, ×10) shows fibroconnective tissue with marked
neutrophilic infiltration and focal necrosis. (b) Penile biopsy (H and E, ×40) shows
numerous admixed myelocytes and metamyelocytes
He was started on hydroxyurea (50 mg/kg/day), intravenous hydration (3 L/m2), and
daily leukapheresis (total five sessions). He also required opioid analgesics to relieve
his pain but with little benefits. Penile aspiration with a large-bore needle was
performed on three occasions to decrease penile swelling. There was a gradual decline
in total leukocyte count over 5 days, but in view of persistent penile swelling and
pain, he underwent surgery for distal penile shunt (corpus cavernosa–glans shunt).
After 7 days of hospital stay and continued symptomatic care, his penile swelling
and pain gradually reduced, and the opioid was discontinued. His WBC was 24 × 109/L
on day 8 of hospital stay. Hydroxyurea and leukopheresis were discontinued, and imatinib
400 mg once a day was started after confirming the diagnosis of CML-CP. He had a complete
hematological response after 3 weeks of therapy and a suboptimal molecular response
at 3 months of imatinib (BCR-ABL transcript 15%). A kinase domain mutation assay was
negative, and he was nonaffording for second-generation TKI, and therefore, continued
on imatinib albeit at a higher dose of 800 mg daily. He achieved major molecular response
at 18 months. Two years since the diagnosis, he offers no complaint except moderate
erectile dysfunction (International Index of Erectile Function [IIFE] score 11), but
he can ejaculate and has been blessed with a son 2 months back.
Discussion
Priapism is defined as persistent (>4 h), painful erection of the penis in the absence
of sexual stimulation. Priapism is classified as low flow (ischemic) and high flow
(nonischemic). Low-flow priapism involves poor muscle contraction resulting in venous
congestion and is commonly caused by intracavernosal injections for impotence or erectile
dysfunction. Other causes include sickle cell disease, hematological malignancy, malignant
infiltration of the penis, drugs, and alcohol. High-flow priapism is usually associated
with trauma, either blunt trauma to the perineum or iatrogenic during local injection
of urological procedure creating a shunt resulting in an excess flow of oxygenated
blood. All cases of priapism must be considered as medical emergencies, particularly
low-flow priapism, which has a worse prognosis with 50% of cases developing subsequent
impotence.
In CML, priapism is seen as the initial presentation, and usually patients have a
history of recurrent episodes of self-remitting priapism (stuttering priapism) before
reporting to the physician. The mechanism of priapism in CML is thought to be due
to leukostasis and hyperviscosity. Therefore, such patients may also have other features
of hyperviscosity in the form of hearing difficulty, breathlessness, visual blurring,
or giddiness.[6]
Unlike the other common complications of CML, priapism is more commonly seen in chronic
phase than in blast crisis. Therefore, the response to first-generation TKI is optimal.[7] The treatment modalities recommended include immediate medical management (hydroxyurea
and analgesia), hydration, and TKI (imatinib) (on confirmation of CML).[8] Apart from systemic treatment, it has been described that local intracavernous therapy
in the form of penile aspiration, instillation of sympathomimetic drugs such as phenylephrine,
and penile shunt procedures are also beneficial in bringing down the penile swelling.[9],[10] Penile biopsy is not recommended in CML with priapism. In the index case, penile
biopsy was the tissue which was obtained during shunt (corpus cavernosa–glans shunt)
surgery for the priapism.
The erectile dysfunction in the index patient as measured by the IIEF-5 score was
23 (i.e., no erectile dysfunction) before and 11 (moderate erectile dysfunction) after
the episode of priapism.[11],[12] However, it is pertinent to note that potency and fertility were preserved although
he presented late (5 days) after the onset of priapism. The reported incidence of
impotence on detumescence in patients presenting late with low-flow priapism is >50%.[8] The present finding suggests that though priapism is low flow (ischemic) in CML,
it has a milder phenotype and better outcome in comparison to other types of low-flow
priapism.
Conclusion
We conclude that although detection of priapism as the presenting manifestation of
CML is rare, it is a medical emergency, putting male patients at risk for developing
significant erectile dysfunction, affecting the quality of life. In the modern era
of TKI, where the life expectancy of CML-CP is comparable to that of the healthy population,
the importance of awareness regarding intensive management of priapism is an absolute
necessity to preserve the quality and productivity of young males.
Informed consent
Informed signed written consent was taken from the patient involved.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form, the patient has given his consent for his images and other clinical information
to be reported in the journal. The patient understands that his name and initials
will not be published, and due efforts will be made to conceal identity, but anonymity
cannot be guaranteed.
